Herbicidal compounds

ABSTRACT

The present invention relates to compounds of Formula (I) or an agronomically acceptable salt of said compounds wherein Q, R 1 , R 2 , n and m are as defined herein. The invention further relates to herbicidal compositions which comprise a compound of Formula (I) and to the use of compounds of Formula (I) for controlling weeds, in particular in crops of useful plants.

The present invention relates to novel herbicidal compounds, toprocesses for their preparation, to herbicidal compositions whichcomprise the novel compounds, and to their use for controlling weeds, inparticular in crops of useful plants, or for inhibiting plant growth.

Herbicidal heteroaryl-substituted phenoxypyrimidines are disclosed in,for example, WO94/17059, WO2015/089003 and WO2015/108779. The presentinvention relates to novel herbicidal phenoxypyridine compounds whichshow improved properties compared to the known pyrimidinecompounds—especially improved crop selectivity.

Thus, according to the present invention there is provided a compound ofFormula (I):

-   -   or an agronomically acceptable salt thereof,    -   wherein    -   Q is a 5-membered aromatic heterocyclic ring which is optionally        substituted by 1 or 2 R³ substituents independently selected        from the group consisting of C₁-C₄alkyl, C₂-C₄alkenyl,        C₂-C₄alkynyl, cyclopropyl, C₁-C₄haloalkyl, C₁-C₂alkoxy-,        C₁-C₂haloalkoxy-, halogen, —C(O)C₁-C₄alkyl, NO₂, —CH₂CN, —CN and        —S(O)_(p)C₁-C₄alkyl;    -   each R¹ is independently selected from the group consisting of        halogen, —CN, nitro, C₁-C₄alkyl, C₂-C₄alkenyl, C₂-C₄alkynyl,        C₁-C₄haloalkyl, C₁-C₄alkoxy-, C₁-C₄haloalkoxy- and        —S(O)_(p)C₁-C₄alkyl;    -   each R² is independently selected from the group consisting of        halogen, —CN, NO₂, C₁-C₄alkyl, C₁-C₄haloalkyl, C₃-C₆cycloalkyl        C₂-C₄alkenyl, C₂-C₄alkynyl, —S(O)_(p)C₁-C₄alkyl, C₁-C₄alkoxy,        —C(O)C₁-C₄alkyl, —C(O)C₁-C₄alkyl and C₁-C₄haloalkoxy;    -   m=0, 1 or 2;    -   n=0, 1 or 2; and    -   p=0, 1 or 2    -   with the proviso that Q is not 1,3,4-oxadiazol-2-yl or a        C-linked tetrazolyl and wherein if Q is 2-thienyl or 2-furyl        then said 2-thienyl or 2-furyl is substituted by 1 or 2 R³        independently selected from the group consisting of        C₁-C₂haloalkyl, halogen and —CN.

C₁-C₄alkyl- includes, for example, methyl (Me, CH₃), ethyl (Et, C₂H₅),n-propyl (n-Pr), isopropyl (i-Pr), n-butyl (n-Bu), isobutyl (i-Bu),sec-butyl and tert-butyl (t-Bu). C₁-C₂alkyl is methyl (Me, CH₃) or ethyl(Et, C₂H₅).

Halogen (or halo) includes, for example, fluorine, chlorine, bromine oriodine. The same correspondingly applies to halogen in the context ofother definitions, such as haloalkyl.

C₁-C₄haloalkyl- includes, for example, fluoromethyl, difluoromethyl,trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl,2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl,1,1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoropropyl and2,2,2-trichloroethyl, heptafluoro-n-propyl and perfluoro-n-hexyl.C₁-C₂haloalkyl is, for example, fluoromethyl, difluoromethyl,trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl,2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, or1,1-difluoro-2,2,2-trichloroethyl.

C₁-C₂alkoxy is methoxy or ethoxy.

C₁-C₂haloalkoxy- includes, for example, fluoromethoxy, difluoromethoxy,trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy,2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy or2,2,2-trichloroethoxy, preferably difluoromethoxy, 2-chloroethoxy ortrifluoromethoxy.

C₃-C₆cycloalkyl- includes cyclopropyl (c-propyl (c-Pr)), cyclobutyl(c-butyl (c-Bu)), cyclopentyl (c-pentyl) and cyclohexyl (c-hexyl).

C₂-C₄alkenyl- includes, for example, —CH═CH₂ (vinyl) and —CH₂—CH═CH₂(allyl).

C₂-C₄alkynyl- includes, for example, —C≡CH (ethynyl) and —CH₂—C≡CH(propargyl).

C₁-C₄alkyl-S— (alkylthio) includes, for example, methylthio, ethylthio,propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio ortert-butylthio, preferably methylthio or ethylthio.

C₁-C₄alkyl-S(O)— (alkylsulfinyl) includes, for example, methylsulfinyl,ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl,isobutylsulfinyl, sec-butylsulfinyl or tert-butylsulfinyl, preferablymethylsulfinyl or ethylsulfinyl.

C₁-C₄alkyl-S(O)₂— (alkylsulfonyl) includes, for example, methylsulfonyl,ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl,isobutylsulfonyl, sec-butylsulfonyl or tert-butylsulfonyl, preferablymethylsulfonyl or ethylsulfonyl.

In one embodiment of the present invention there is provided a compoundof Formula (I) wherein n is 0. In another embodiment of the presentinvention there is provided a compound of Formula (I) wherein n is 1 or2 and each R¹ is independently selected from the group consisting ofhalogen, —CN, nitro, C₁-C₂alkyl, C₁-C₂haloalkyl, C₁-C₂alkoxy andC₁-C₂haloalkoxy-. In a preferred embodiment of the present inventionthere is provided a compound of Formula (I) wherein n is 1 and R¹ ishalogen (especially fluoro, chloro or bromo) or CN. In an especiallypreferred embodiment of the present invention there is provided acompound of Formula (I) wherein n is 1 and R¹ is fluoro, especially3-fluoro.

In another embodiment of the present invention there is provided acompound of Formula (I), wherein m=0. In another embodiment of thepresent invention there is provided a compound of Formula (I) wherein mis 1 or 2. In a preferred embodiment of the present invention there isprovided a compound of Formula (I) wherein m is 1 or 2 and each R² isindependently selected from the group consisting of halogen (especiallyfluoro, chloro or bromo), nitro, —CN and C₁-C₄haloalkyl (especiallytrifluoromethyl). In a particularly preferred embodiment of the presentinvention there is provided a compound of Formula (I) wherein m is 1 or2 and each R² is independently selected from the group consisting offluoro, chloro, bromo, nitro, —CN and trifluoromethyl.

In another embodiment of the present invention there is provided acompound of Formula (I) wherein Q is selected from the group consistingof:

wherein R³ is selected from the group consisting of hydrogen,C₁-C₄alkyl, C₂-C₄alkenyl, C₂-C₄alkynyl, cyclopropyl, C₁-C₂haloalkyl,C₁-C₂alkoxy-, C₁-C₂haloalkoxy-, halogen, —C(O)C₁-C₄alkyl, NO₂, —CH₂CN,—CN and —S(O)_(p)C₁-C₄alkyl; and

R^(3a) is hydrogen or C₁-C₂alkyl.

In a preferred embodiment of the present invention, Q is Q19, Q20 orQ34.

In another embodiment of the present invention there is provided acompound of Formula (I), wherein R³ is C₁-C₂haloalkyl. In a morepreferred embodiment R³ is difluoromethyl or trifluoromethyl.

Thus, in a preferred embodiment of the present invention the compound ofFormula (I) is a compound of Formula (Ia):

wherein R¹ is hydrogen, fluoro, chloro, bromo or CN and R², m and R³ areas defined previously.

In another preferred embodiment of the present invention the compound ofFormula (I) is a compound of Formula (Ib):

wherein R¹ is hydrogen, fluoro, chloro, bromo or CN and R², m and R³ areas defined previously.

In another preferred embodiment of the present invention the compound ofFormula (I) is a compound of Formula (Ic):

wherein R¹ is hydrogen, fluoro, chloro, bromo or CN and R², m and R³ areas defined previously.

Compounds of Formula (I) may contain asymmetric centres and may bepresent as a single enantiomer, pairs of enantiomers in any proportionor, where more than one asymmetric centre are present, containdiastereoisomers in all possible ratios. Typically one of theenantiomers has enhanced biological activity compared to the otherpossibilities.

The present invention also provides agronomically acceptable salts ofcompounds of Formula (I). Salts that the compounds of Formula (I) mayform with amines, including primary, secondary and tertiary amines (forexample ammonia, dimethylamine and triethylamine), alkali metal andalkaline earth metal bases, transition metals or quaternary ammoniumbases are preferred.

The compounds of Formula (I) according to the invention can be used asherbicides by themselves, but they are generally formulated intoherbicidal compositions using formulation adjuvants, such as carriers,solvents and surface-active agents (SAA). Thus, the present inventionfurther provides a herbicidal composition comprising a herbicidalcompound according to any one of the previous claims and anagriculturally acceptable formulation adjuvant. The composition can bein the form of concentrates which are diluted prior to use, althoughready-to-use compositions can also be made. The final dilution isusually made with water, but can be made instead of, or in addition to,water, with, for example, liquid fertilisers, micronutrients, biologicalorganisms, oil or solvents.

The herbicidal compositions generally comprise from 0.1 to 99% byweight, especially from 0.1 to 95% by weight, compounds of Formula I andfrom 1 to 99.9% by weight of a formulation adjuvant which preferablyincludes from 0 to 25% by weight of a surface-active substance.

The compositions can be chosen from a number of formulation types. Theseinclude an emulsion concentrate (EC), a suspension concentrate (SC), asuspo-emulsion (SE), a capsule suspension (CS), a water dispersiblegranule (WG), an emulsifiable granule (EG), an emulsion, water in oil(EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oildispersion (OD), an oil miscible flowable (OF), an oil miscible liquid(OL), a soluble concentrate (SL), an ultra-low volume suspension (SU),an ultra-low volume liquid (UL), a technical concentrate (TK), adispersible concentrate (DC), a soluble powder (SP), a wettable powder(WP) and a soluble granule (SG). The formulation type chosen in anyinstance will depend upon the particular purpose envisaged and thephysical, chemical and biological properties of the compound of Formula(I).

Soluble powders (SP) may be prepared by mixing a compound of Formula (I)with one or more water-soluble inorganic salts (such as sodiumbicarbonate, sodium carbonate or magnesium sulphate) or one or morewater-soluble organic solids (such as a polysaccharide) and, optionally,one or more wetting agents, one or more dispersing agents or a mixtureof said agents to improve water dispersibility/solubility. The mixtureis then ground to a fine powder. Similar compositions may also begranulated to form water soluble granules (SG).

Wettable powders (WP) may be prepared by mixing a compound of Formula(I) with one or more solid diluents or carriers, one or more wettingagents and, preferably, one or more dispersing agents and, optionally,one or more suspending agents to facilitate the dispersion in liquids.The mixture is then ground to a fine powder. Similar compositions mayalso be granulated to form water dispersible granules (WG).

Granules (GR) may be formed either by granulating a mixture of acompound of Formula (I) and one or more powdered solid diluents orcarriers, or from pre-formed blank granules by absorbing a compound ofFormula (I) (or a solution thereof, in a suitable agent) in a porousgranular material (such as pumice, attapulgite clays, fuller's earth,kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing acompound of Formula (I) (or a solution thereof, in a suitable agent) onto a hard core material (such as sands, silicates, mineral carbonates,sulphates or phosphates) and drying if necessary. Agents which arecommonly used to aid absorption or adsorption include solvents (such asaliphatic and aromatic petroleum solvents, alcohols, ethers, ketones andesters) and sticking agents (such as polyvinyl acetates, polyvinylalcohols, dextrins, sugars and vegetable oils). One or more otheradditives may also be included in granules (for example an emulsifyingagent, wetting agent or dispersing agent).

Dispersible Concentrates (DC) may be prepared by dissolving a compoundof Formula (I) in water or an organic solvent, such as a ketone, alcoholor glycol ether. These solutions may contain a surface active agent (forexample to improve water dilution or prevent crystallisation in a spraytank).

Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may beprepared by dissolving a compound of Formula (I) in an organic solvent(optionally containing one or more wetting agents, one or moreemulsifying agents or a mixture of said agents). Suitable organicsolvents for use in ECs include aromatic hydrocarbons (such asalkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100,SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark),ketones (such as cyclohexanone or methylcyclohexanone) and alcohols(such as benzyl alcohol, furfuryl alcohol or butanol),N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone),dimethyl amides of fatty acids (such as C₈-C₁₀ fatty acid dimethylamide)and chlorinated hydrocarbons. An EC product may spontaneously emulsifyon addition to water, to produce an emulsion with sufficient stabilityto allow spray application through appropriate equipment.

Preparation of an EW involves obtaining a compound of Formula (I) eitheras a liquid (if it is not a liquid at room temperature, it may be meltedat a reasonable temperature, typically below 70° C.) or in solution (bydissolving it in an appropriate solvent) and then emulsifying theresultant liquid or solution into water containing one or more SAAs,under high shear, to produce an emulsion. Suitable solvents for use inEWs include vegetable oils, chlorinated hydrocarbons (such aschlorobenzenes), aromatic solvents (such as alkylbenzenes oralkylnaphthalenes) and other appropriate organic solvents which have alow solubility in water.

Microemulsions (ME) may be prepared by mixing water with a blend of oneor more solvents with one or more SAAs, to produce spontaneously athermodynamically stable isotropic liquid formulation. A compound ofFormula (I) is present initially in either the water or the solvent/SAAblend. Suitable solvents for use in MEs include those hereinbeforedescribed for use in in ECs or in EWs. An ME may be either anoil-in-water or a water-in-oil system (which system is present may bedetermined by conductivity measurements) and may be suitable for mixingwater-soluble and oil-soluble pesticides in the same formulation. An MEis suitable for dilution into water, either remaining as a microemulsionor forming a conventional oil-in-water emulsion.

Suspension concentrates (SC) may comprise aqueous or non-aqueoussuspensions of finely divided insoluble solid particles of a compound ofFormula (I). SCs may be prepared by ball or bead milling the solidcompound of Formula (I) in a suitable medium, optionally with one ormore dispersing agents, to produce a fine particle suspension of thecompound. One or more wetting agents may be included in the compositionand a suspending agent may be included to reduce the rate at which theparticles settle. Alternatively, a compound of Formula (I) may be drymilled and added to water, containing agents hereinbefore described, toproduce the desired end product.

Aerosol formulations comprise a compound of Formula (I) and a suitablepropellant (for example n-butane). A compound of Formula (I) may also bedissolved or dispersed in a suitable medium (for example water or awater miscible liquid, such as n-propanol) to provide compositions foruse in non-pressurised, hand-actuated spray pumps.

Capsule suspensions (CS) may be prepared in a manner similar to thepreparation of EW formulations but with an additional polymerisationstage such that an aqueous dispersion of oil droplets is obtained, inwhich each oil droplet is encapsulated by a polymeric shell and containsa compound of Formula (I) and, optionally, a carrier or diluenttherefor. The polymeric shell may be produced by either an interfacialpolycondensation reaction or by a coacervation procedure. Thecompositions may provide for controlled release of the compound ofFormula (I) and they may be used for seed treatment. A compound ofFormula (I) may also be formulated in a biodegradable polymeric matrixto provide a slow, controlled release of the compound.

The composition may include one or more additives to improve thebiological performance of the composition, for example by improvingwetting, retention or distribution on surfaces; resistance to rain ontreated surfaces; or uptake or mobility of a compound of Formula (I).Such additives include surface active agents (SAAs), spray additivesbased on oils, for example certain mineral oils or natural plant oils(such as soy bean and rape seed oil), modified plant oils such asmethylated rape seed oil (MRSO), and blends of these with otherbio-enhancing adjuvants (ingredients which may aid or modify the actionof a compound of Formula (I).

Wetting agents, dispersing agents and emulsifying agents may be SAAs ofthe cationic, anionic, amphoteric or non-ionic type.

Suitable SAAs of the cationic type include quaternary ammonium compounds(for example cetyltrimethyl ammonium bromide), imidazolines and aminesalts.

Suitable anionic SAAs include alkali metals salts of fatty acids, saltsof aliphatic monoesters of sulphuric acid (for example sodium laurylsulphate), salts of sulphonated aromatic compounds (for example sodiumdodecylbenzenesulphonate, calcium dodecylbenzenesulphonate,butylnaphthalene sulphonate and mixtures of sodium di-isopropyl- andtri-isopropyl-naphthalene sulphonates), ether sulphates, alcohol ethersulphates (for example sodium laureth-3-sulphate), ether carboxylates(for example sodium laureth-3-carboxylate), phosphate esters (productsfrom the reaction between one or more fatty alcohols and phosphoric acid(predominately mono-esters) or phosphorus pentoxide (predominatelydi-esters), for example the reaction between lauryl alcohol andtetraphosphoric acid; additionally these products may be ethoxylated),sulphosuccinamates, paraffin or olefine sulphonates, taurates,lignosulphonates and phosphates/sulphates of tristyrylphenols.

Suitable SAAs of the amphoteric type include betaines, propionates andglycinates.

Suitable SAAs of the non-ionic type include condensation products ofalkylene oxides, such as ethylene oxide, propylene oxide, butylene oxideor mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetylalcohol) or with alkylphenols (such as octylphenol, nonylphenol oroctylcresol); partial esters derived from long chain fatty acids orhexitol anhydrides; condensation products of said partial esters withethylene oxide; block polymers (comprising ethylene oxide and propyleneoxide); alkanolamides; simple esters (for example fatty acidpolyethylene glycol esters); amine oxides (for example lauryl dimethylamine oxide); lecithins and sorbitans and esters thereof, alkylpolyglycosides and tristyrylphenols.

Suitable suspending agents include hydrophilic colloids (such aspolysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose)and swelling clays (such as bentonite or attapulgite).

The herbicidal compounds of present invention can also be used inmixture with one or more additional herbicides and/or plant growthregulators. Examples of such additional herbicides or plant growthregulators include acetochlor, acifluorfen (includingacifluorfen-sodium), aclonifen, ametryn, amicarbazone, aminopyralid,aminotriazole, atrazine, bensulfuron (including bensulfuron-methyl),bentazone, bicyclopyrone, bilanafos, bispyribac-sodium, bixlozone,bromacil, bromoxynil, butachlor, butafenacil, carfentrazone (includingcarfentrazone-ethyl), cloransulam (including cloransulam-methyl),chlorimuron (including chlorimuron-ethyl), chlorotoluron, chlorsulfuron,cinmethylin, clacyfos, clethodim, clodinafop (includingclodinafop-propargyl), clomazone, clopyralid, cyclopyranil,cyclopyrimorate, cyclosulfamuron, cyhalofop (including cyhalofop-butyl),2,4-D (including the choline salt and 2-ethylhexyl ester thereof),2,4-DB, desmedipham, dicamba (including the aluminium, aminopropyl,bis-aminopropylmethyl, choline, dichloroprop, diglycolamine,dimethylamine, dimethylammonium, potassium and sodium salts thereof)diclosulam, diflufenican, diflufenzopyr, dimethachlor, dimethenamid-P,diquat dibromide, diuron, ethalfluralin, ethofumesate, fenoxaprop(including fenoxaprop-P-ethyl), fenoxasulfone, fenquinotrione,fentrazamide, flazasulfuron, florasulam, florpyrauxifen (includingflorpyraxifen-benzyl), fluazifop (including fluazifop-P-butyl),flucarbazone (including flucarbazone-sodium), flufenacet, flumetsulam,flumioxazin, flupyrsulfuron (including flupyrsulfuron-methyl-sodium),fluroxypyr (including fluroxypyr-meptyl), fomesafen, foramsulfuron,glufosinate (including the ammonium salt thereof), glyphosate (includingthe diammonium, isopropylammonium and potassium salts thereof),halauxifen (including halauxifen-methyl), haloxyfop (includinghaloxyfop-methyl), hexazinone, hydantocidin, imazamox, imazapic,imazapyr, imazethapyr, indaziflam, iodosulfuron (includingiodosulfuron-methyl-sodium), iofensulfuron (includingiofensulfuron-sodium), ioxynil, isoproturon, isoxaflutole, lancotrione,MCPA, MCPB, mecoprop-P, mesosulfuron (including mesosulfuron-methyl),mesotrione, metamitron, metazachlor, methiozolin, metolachlor,metosulam, metribuzin, metsulfuron, napropamide, nicosulfuron,norflurazon, oxadiazon, oxasulfuron, oxyfluorfen, paraquat dichloride,pendimethalin, penoxsulam, phenmedipham, picloram, pinoxaden,pretilachlor, primisulfuron-methyl, propanil, propaquizafop,propyrisulfuron, propyzamide, prosulfocarb, prosulfuron, pyraclonil,pyraflufen (including pyraflufen-ethyl), pyrasulfotole, pyridate,pyriftalid, pyrimisulfan, pyroxasulfone, pyroxsulam, quinclorac,quinmerac, quizalofop (including quizalofop-P-ethyl andquizalofop-P-tefuryl), rimsulfuron, saflufenacil, sethoxydim, simazine,S-metalochlor, sulfentrazone, sulfosulfuron, tebuthiuron, tefuryltrione,tembotrione, terbuthylazine, terbutryn, thiencarbazone, thifensulfuron,tiafenacil, tolpyralate, topramezone, tralkoxydim, triafamone,triallate, triasulfuron, tribenuron (including tribenuron-methyl),triclopyr, trifloxysulfuron (including trifloxysulfuron-sodium),trifludimoxazin, trifluralin, triflusulfuron,4-hydroxy-1-methoxy-5-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one,4-hydroxy-1,5-dimethyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one,5-ethoxy-4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one,4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one,4-hydroxy-1,5-dimethyl-3-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]imidazolidin-2-one,(4R)1-(5-tert-butylisoxazol-3-yl)-4-ethoxy-5-hydroxy-3-methyl-imidazolidin-2-one,3-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]bicyclo[3.2.1]octane-2,4-dione,2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-5-methyl-cyclohexane-1,3-dione,2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]cyclohexane-1,3-dione,2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-5,5-dimethyl-cyclohexane-1,3-dione,6-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-2,2,4,4-tetramethyl-cyclohexane-1,3,5-trione,2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-5-ethyl-cyclohexane-1,3-dione,2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-4,4,6,6-tetramethyl-cyclohexane-1,3-dione,2-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-5-methyl-cyclohexane-1,3-dione,3-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]bicyclo[3.2.1]octane-2,4-dione,2-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-5,5-dimethyl-cyclohexane-1,3-dione,6-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-2,2,4,4-tetramethyl-cyclohexane-1,3,5-trione,2-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]cyclohexane-1,3-dione,4-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-2,2,6,6-tetramethyl-tetrahydropyran-3,5-dioneand4-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-2,2,6,6-tetramethyl-tetrahydropyran-3,5-dione.

The mixing partners of the compound of Formula (I) may also be in theform of esters or salts, as mentioned e.g. in The Pesticide Manual,Sixteenth Edition, British Crop Protection Council, 2012.

The compound of Formula (I) can also be used in mixtures with otheragrochemicals such as fungicides, nematicides or insecticides, examplesof which are given in The Pesticide Manual.

The mixing ratio of the compound of Formula (I) to the mixing partner ispreferably from 1:100 to 1000:1.

The mixtures can advantageously be used in the above-mentionedformulations (in which case “active ingredient” relates to therespective mixture of compound of Formula (I) with the mixing partner).

The compounds or mixtures of the present invention can also be used incombination with one or more herbicide safeners. Examples of suchsafeners include benoxacor, cloquintocet (including cloquintocet-mexyl),cyprosulfamide, dichlormid, fenchlorazole (includingfenchlorazole-ethyl), fenclorim, fluxofenim, furilazole, isoxadifen(including isoxadifen-ethyl), mefenpyr (including mefenpyr-diethyl),metcamifen and oxabetrinil.

Particularly preferred are mixtures of a compound of Formula (I) withcyprosulfamide, isoxadifen-ethyl, cloquintocet-mexyl and/orN-(2-methoxybenzoyl)-4-[(methyl-aminocarbonyl)amino]benzenesulfonamide.

The safeners of the compound of Formula (I) may also be in the form ofesters or salts, as mentioned e.g. in The Pesticide Manual, 16^(th)Edition (BCPC), 2012. The reference to cloquintocet-mexyl also appliesto a lithium, sodium, potassium, calcium, magnesium, aluminium, iron,ammonium, quaternary ammonium, sulfonium or phosphonium salt thereof asdisclosed in WO 02/34048.

Preferably the mixing ratio of compound of Formula (I) to safener isfrom 100:1 to 1:10, especially from 20:1 to 1:1.

The present invention still further provides a method of controllingweeds at a locus said method comprising application to the locus of aweed controlling amount of a composition comprising a compound ofFormula (I). Moreover, the present invention may further provide amethod of selectively controlling weeds at a locus comprising cropplants and weeds, wherein the method comprises application to the locusof a weed controlling amount of a composition according to the presentinvention. ‘Controlling’ means killing, reducing or retarding growth orpreventing or reducing germination. It is noted that the compounds ofthe present invention show a much improved selectivity compared to know,structurally similar compounds. Generally the plants to be controlledare unwanted plants (weeds). ‘Locus’ means the area in which the plantsare growing or will grow. The application may be applied to the locuspre-emergence and/or postemergence of the crop plant. Some crop plantsmay be inherently tolerant to herbicidal effects of compounds of Formula(I). Preferred crop plants include maize, wheat, barley and rice.

The rates of application of compounds of Formula I may vary within widelimits and depend on the nature of the soil, the method of application(pre- or post-emergence; seed dressing; application to the seed furrow;no tillage application etc.), the crop plant, the weed(s) to becontrolled, the prevailing climatic conditions, and other factorsgoverned by the method of application, the time of application and thetarget crop. The compounds of Formula I according to the invention aregenerally applied at a rate of from 10 to 2500 g/ha, especially from 25to 1000 g/ha, more especially from 25 to 250 g/ha.

The application is generally made by spraying the composition, typicallyby tractor mounted sprayer for large areas, but other methods such asdusting (for powders), drip or drench can also be used.

Crop plants are to be understood as also including those crop plantswhich have been rendered tolerant to other herbicides or classes ofherbicides (e.g. ALS-, GS-, EPSPS-, PPO-, HPPD-, -PDS andACCase-inhibitors) by conventional methods of breeding or by geneticengineering. An example of a crop that has been rendered tolerant toimidazolinones, e.g. imazamox, by conventional methods of breeding isClearfield® summer rape (canola). Examples of crops that have beenrendered tolerant to herbicides by genetic engineering methods includee.g. glyphosate- and glufosinate-resistant maize varieties commerciallyavailable under the trade names RoundupReady® and LibertyLink®.

Crop plants are also to be understood as being those which have beenrendered resistant to harmful insects by genetic engineering methods,for example Bt maize (resistant to European corn borer), Bt cotton(resistant to cotton boll weevil) and also Bt potatoes (resistant toColorado beetle). Examples of Bt maize are the Bt 176 maize hybrids ofNK® (Syngenta Seeds). The Bt toxin is a protein that is formed naturallyby Bacillus thuringiensis soil bacteria. Examples of toxins, ortransgenic plants able to synthesise such toxins, are described inEP-A-451 878, EP-A-374 753, WO 93/07278, WO 95/34656, WO 03/052073 andEP-A-427 529. Examples of transgenic plants comprising one or more genesthat code for an insecticidal resistance and express one or more toxinsare KnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton),Bollgard® (cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®.Plant crops or seed material thereof can be both resistant to herbicidesand, at the same time, resistant to insect feeding (“stacked” transgenicevents). For example, seed can have the ability to express aninsecticidal Cry3 protein while at the same time being tolerant toglyphosate.

Crop plants are also to be understood to include those which areobtained by conventional methods of breeding or genetic engineering andcontain so-called output traits (e.g. improved storage stability, highernutritional value and improved flavour).

The compositions can be used to control unwanted plants (collectively,‘weeds’). The weeds to be controlled may be both monocotyledonousspecies, for example Agrostis, Alopecurus, Avena, Brachiaria, Bromus,Cenchrus, Cyperus, Digitaria, Echinochloa, Eleusine, Lolium, Monochoria,Rottboellia, Sagittaria, Scirpus, Setaria and Sorghum, anddicotyledonous species, for example Abutilon, Amaranthus, Ambrosia,Chenopodium, Chrysanthemum, Conyza, Galium, Ipomoea, Nasturtium, Sida,Sinapis, Solanum, Stellaria, Veronica, Viola and Xanthium.

In a further aspect of the present invention there is provided the useof a compound of Formula (I) as defined herein as a herbicide.

The compounds of the present invention can be prepared according to thefollowing schemes.

Processes for Preparation of Compounds of Formula (I)

Processes for preparation of compounds, e.g. a compound of formula (I)(which optionally can be an agrochemically acceptable salt thereof), arenow described, and form further aspects of the present invention.

A compound of Formula I may be prepared from a compound of Formula A byreaction with a compound of Formula B (where LG represents a suitableleaving group such as Br, Cl, F or OSC₂Me) optionally in the presence ofa suitable base and in a suitable solvent at a suitable reactiontemperature. Suitable bases may include K₂CO₃ or Cs₂CO₃. Suitablesolvents include DMF. Suitable reaction temperatures are between 20° C.and 120° C. Compounds of Formula B are commercially available or may beprepared by methods known in the literature.

Alternatively, a compound of Formula A may be prepared from a compoundof Formula C (where PG represents a suitable protecting group, such asMe or Ac) via a deprotection reaction. Suitable conditions fordeprotection when PG=Me include the use of BBr₃ in a suitable solvent,such as DCM. Suitable condition for deprotection when PG=Ac include theuse of K₂CO₃ or NH₄OAC in a suitable solvent, such as MeOH or MeOH/H₂O.

A compound of Formula C may be prepared from a compound of Formula D(where X represents a suitable halogen such as F, Cl, Br or I or asuitable pseudohalogen such as OTf) via reaction with a compound ofFormula E (where Y represents a suitable coupling partner functionalgroup such as —B(OR)₂ or —SnR₃) in the presence of a suitablecatalyst/ligand combination, optionally in the presence of a suitablebase and in a suitable solvent. Suitable catalysts may includebis-triphenylphosphine-palladium(II) chloride. Suitable bases mayinclude CS₂CO₃. Suitable solvents may include 1,4-dioxane or DMF.Compounds of Formula D and of Formula E are commercially available ormay be prepared by methods known in the literature.

In an alternative approach, a compound of Formula C may be prepared froma compound of Formula F (where Y represents a suitable coupling partnerfunctional group such as —B(OR)₂ or —SnR₃) and a compound of Formula G(where Q is a C-linked heterocycle such as Q1 and Q2 and where Xrepresents a suitable halogen such as F, Cl, Br or I or a suitablepseudohalogen such as OTf) in the presence of a suitable catalyst/ligandcombination, optionally in the presence of a suitable base and in asuitable solvent. Suitable catalysts may includetetrakis(triphenylphosphine) palladium. Suitable bases may includeK₂CO₃. Suitable solvents may include DCM/H₂O. Compounds of Formula F andof Formula G are commercially available or may be prepared by methodsknown in the literature.

In an alternative approach, a compound of Formula I may be prepared froma compound of Formula H (where X represents a suitable halogen such asF, Cl, Br or I or a suitable pseudohalogen such as OTf) and a compoundof Formula E (where Y represents a suitable coupling partner functionalgroup such as —B(OR)₂ or —SnR₃) in the presence of a suitablecatalyst/ligand combination, optionally in the presence of a suitablebase and in a suitable solvent. Suitable catalysts may includebis-triphenylphosphine-palladium(II) chloride. Suitable bases mayinclude CS₂CO₃. Suitable solvents may include 1,4-dioxane or DMF.Compounds of Formula E are commercially available or may be prepared bymethods known in the literature.

A compound of Formula H may be prepared from a compound of Formula J anda compound of Formula B (where LG represents a suitable leaving groupsuch as Br, Cl, F or OSO₂Me) in the presence of a suitable base and in asuitable solvent.

Suitable bases may include CS₂CO₃, K₂CO₃ or NaH. Suitable solvents mayinclude DMF or DMSO. Compounds of Formula J and of Formula B arecommercially available or may be prepared by methods known in theliterature.

In a further alternative approach, a compound of Formula I may beprepared from a compound of Formula K (where Y represents a suitablecoupling partner functional group such as —B(OR)₂ or —SnR₃) and acompound of Formula G (where Q is a C-linked heterocycle and where Xrepresents a suitable halogen such as F, Cl, Br or I or a suitablepseudohalogen such as OTf) in the presence of a suitable catalyst/ligandcombination, optionally in the presence of a suitable base and in asuitable solvent. Suitable catalysts may includetetrakis(triphenylphosphine) palladium. Suitable bases may includeK₂CO₃. Suitable solvents may include DCM/H₂O. Compounds of Formula G arecommercially available or may be prepared by methods known in theliterature.

A compound of Formula K may be prepared from a compound of Formula L(where Y represents a suitable coupling partner functional group such as—B(OR)₂ or —SnR₃) and a compound of Formula B (where LG represents asuitable leaving group such as Br, Cl, F or OSO₂Me) in the presence of asuitable base and in a suitable solvent. Suitable bases may includeCS₂CO₃, K₂CO₃ or NaH. Suitable solvents may include DMF or DMSO.Compounds of Formula L and of Formula B are commercially available ormay be prepared by methods known in the literature.

In a yet further alternative approach, a compound of Formula I may beprepared from a compound of Formula M (where X represents a suitablehalogen such as F, Cl, Br or I or a suitable pseudohalogen such as OTf)and a compound of Formula N in the presence of a suitable catalyst,optionally in the presence of a suitable base and in a suitable solvent.Suitable catalysts may include copper (I) iodide. Suitable bases mayinclude K₂CO₃. Suitable solvents may include DMSO. Compounds of FormulaM and of Formula N are commercially available or may be prepared bymethods known in the literature.

In a still further alternative approach, a compound of Formula C may beprepared from a compound of Formula P (where J is an alkene, alkyne,oxime, ketone, carboxylic acid, ester, amide, hydrazine, azide or amine)using methods of heterocycle formation known in the literature.

Similarly, a compound of Formula I may be prepared from a compound offormula Q (where J is an alkene, alkyne, oxime, ketone, carboxylic acid,ester, amide, hydrazine, azide or amine) using methods of heterocycleformation known in the literature.

In a further approach, a compound of Formula Ci (a compound of Formula Cwhere Q is a suitable ortho-directing heterocycle such as Q9, Q11, Q12,Q34 or Q35) may be prepared from a compound of Formula R in the presenceof a suitable catalyst, a suitable oxidant and a suitable nucleophile.Suitable catalysts may include Pd(OAc)₂. Suitable oxidants may include(diacetoxyiodo)benzene. Suitable nucleophiles may include acetic acid.

A compound of Formula R may be prepared from a compound of Formula S(where X represents a suitable halogen such as Cl, Br or I or a suitablepseudohalogen such as OTf) via reaction with a compound of Formula E(where Y represents a suitable coupling partner functional group such as—B(OR)₂ or —SnR₃) in the presence of a suitable catalyst/ligandcombination, optionally in the presence of a suitable base and in asuitable solvent. Suitable catalysts may includebis-triphenylphosphine-palladium(II) chloride. Suitable bases mayinclude CS₂CO₃. Suitable solvents may include 1,4-dioxane or DMF.Compounds of Formula S and of Formula E are commercially available ormay be prepared by methods known in the literature.

Alternatively, a compound of Formula R may be prepared from a compoundof Formula T (where Y represents a suitable coupling partner functionalgroup such as —B(OR)₂ or —SnR₃) and a compound of Formula G (where Q isa C-linked heterocycle and where X represents a suitable halogen such asF, Cl, Br or I or a suitable pseudohalogen such as OTf) in the presenceof a suitable catalyst/ligand combination, optionally in the presence ofa suitable base and in a suitable solvent. Suitable catalysts mayinclude tetrakis(triphenylphosphine) palladium. Suitable bases mayinclude K₂CO₃. Suitable solvents may include DCM/H₂O. Compounds ofFormula T and of Formula G are commercially available or may be preparedby methods known in the literature.

In an alternative approach, a compound of Formula Cii (a compound ofFormula C where R^(1-ortho)=halogen and Q is a suitable ortho-directingheterocycle such as Q9, Q11, Q12, Q34 or Q35) may be prepared from acompound of Formula Ciii (a compound of Formula C where R^(1-ortho)=H)via reaction with a suitable halogenation reagent, in the presence of asuitable catalyst and optionally in a suitable solvent. Suitablehalogenation reagents may include N-iodosuccinimide, N-bromosuccinimide,N-chlorosuccinimide or N-Fluorobenzenesulfonimide. Suitable catalystsmay include Pd(OAc)₂. Suitable solvents may include acetic acid.

In yet another alternative approach, a compound of Formula A (where Q isan N-linked heterocycle and R¹ is an electron withdrawing group such ashalogen, CN or NO₂) may be prepared from a compound of Formula U via anS_(N)Ar reaction with a compound of Formula V in the presence of asuitable base and in a suitable solvent. Suitable bases may includeK₂CO₃. Suitable solvents may include N,N-dimethylacetamide. Compounds ofFormula U and of Formula V are commercially available or may be preparedby methods known in the literature.

The following non-limiting examples provide specific synthesis methodsfor representative compounds of the present invention, as referred to inTable 1 below.

EXAMPLE 1: SYNTHESIS OF5-[2-[(5-CHLORO-3-FLUORO-2-PYRIDYL)OXY]-6-FLUORO-PHENYL]-3-(DIFLUOROMETHYL)ISOXAZOLE(A1)

To a stirred solution of2-[3-(difluoromethyl)isoxazol-5-yl]-3-fluoro-phenol (0.06 g, 0.26 mmol)in N-dimethylformamide (1.8 mL) was added K₂CO₃ (0.18 g, 1.3 mmol)followed by 5-chloro-2,3-difluoro-pyridine (0.049 g, 0.33 mmol). Thereaction was stirred overnight at RT and then heated to 80° C. for 4hours. The reaction mixture was cooled to RT, diluted with DCM andacidified with 2M HCl, the phases were separated then the aqueous wasre-extracted with DCM and the combined organics evaporated to drynessunder reduced pressure. The crude residue was purified by flashchromatography on silica gel using a gradient of 0-10% ethyl acetate inisohexane as eluent to give the desired product as a white solid (0.066g, 70%).

¹H NMR (400 MHz, CDCl₃) δ 7.83 (d, 1H), 7.57 (d, 2H), 7.24-7.08 (m, 2H),6.94-6.61 (m, 2H)

EXAMPLE 2: SYNTHESIS OF3-(DIFLUOROMETHYL)-5-[2-FLUORO-6-[(5-NITRO-2-PYRIDYL)OXY]PHENYL]ISOXAZOLE(A2)

To a stirred solution of the2-[3-(difluoromethyl)isoxazol-5-yl]-3-fluoro-phenol (0.06 g, 0.26 mmol)in N,N-dimethylformamide (1.8 mL) was added K₂CO₃ (0.18 g, 1.3 mmol)followed by 2-chloro-5-nitro-pyridine (0.052 g, 0.33 mmol). The reactionwas stirred overnight at RT, then diluted with DCM and acidified with 2MHCl, the phases were separated then the aqueous was re-extracted withDCM and the combined organics evaporated to dryness under reducedpressure. The crude residue was purified by flash chromatography onsilica gel using a gradient of 0-20% ethyl acetate in isohexane aseluent to give the desired product as a colourless oil (0.078 g, 85%).

¹H NMR (400 MHz, CDCl₃) δ 8.95 (d, 1H), 8.64-8.43 (m, 1H), 7.59 (dt,1H), 7.32-7.10 (m, 3H), 6.97-6.53 (m, 2H)

EXAMPLE 3: SYNTHESIS OF2-[2-[(5-CHLORO-3-FLUORO-2-PYRIDYL)OXY]-6-FLUORO-PHENYL]-5-(TRIFLUOROMETHYL)OXAZOLE(A3)

To a stirred solution of3-(2-fluoro-6-hydroxy-phenyl)-5-(trifluoromethyl)-4H-isoxazol-5-ol(0.100 g, 0.377 mmol) in DMF (5 mL) was added K₂CO₃ (0.317 g, 2.26 mmol)and 5-chloro-2,3-difluoropyridine (0.141 g, 0.943 mmol). The reactionwas heated at 80° C. for 4 hours and then allowed to cool to RT. Thereaction mixture was diluted with EtOAc and H₂O, the phases wereseparated and the aqueous phase was extracted with further EtOAc. Thecombined organics were washed with H₂O, dried over MgSO₄ and evaporatedto dryness under reduced pressure. The crude residue was purified byflash chromatography over silica gel using 0-10% EtOAc/isohexane aseluent to give the desired product (0.068 g, 48%) as a pale yellowsolid.

¹H NMR (400 MHz, CDCl₃) δ 7.78 (d, 1H), 7.67-7.42 (m, 3H), 7.24-7.05 (m,2H).

EXAMPLE 4: SYNTHESIS OF5-NITRO-2-[2-[4-(TRIFLUOROMETHYL)PYRAZOL-1-YL]PHENOXY]PYRIDINE (A14)Step 1: Synthesis of 1-(2-methoxyphenyl)-4-(trifluoromethyl)pyrazole

To a stirred solution of l-bromo-2-methoxy-benzene (0.20 g, 1.07 mmol)in 1,4-dioxane (4 mL) was added 4-(trifluoromethyl)-1H-pyrazole (0.291g, 2.14 mmol), CuI (0.204 g, 1.07 mmol), N,N′-dimethylethane-1,2-diamine(0.189 mg, 2.74 mmol) and K₂CO₃ (0.227 g, 1.64 mmol). The reaction washeated at reflux for 72 hours, allowed to cool to room temperature,absorbed onto silica gel and purified by flash chromatography on silicagel using a gradient of 5-50% EtOAc in isohexane as eluent to give thedesired product (0.169 g, 65%) as a colourless oil.

¹H NMR (400 MHz, CDCl₃) δ 8.31 (s, 1H), 7.88 (s, 1H), 7.72 (d, 1H), 7.36(t, 1H), 7.11-7.03 (m, 2H), 3.91 (s, 3H).

Step 2: Synthesis of 2-[4-(trifluoromethyl)pyrazol-1-yl]phenol

To a stirred solution of 1-(2-methoxyphenyl)-4-(trifluoromethyl)pyrazole(1.25 g, 5.16 mmol) in DCM (100 mL) at 0° C. under an atmosphere of N₂was added BBr₃ (12.9 mL of a 1M solution in DCM, 12.9 mmol). Thereaction mixture was allowed to warm to 15° C. over 2 hours, quenchedwith water, the pH adjusted to 7 with saturated NaHCO₃ solution andextracted with DCM (×3). The combined organic extracts were washed withbrine, dried over MgSO₄, absorbed onto silica gel and purified by flashchromatography on silica gel using a gradient of 5-50% EtOAc inisohexane as eluent to give the desired product (1.06 g, 90%) as a whitesolid.

¹H NMR (400 MHz, CDCl₃) δ 10.50 (s, 1H), 8.28 (s, 1H), 7.94 (s, 1H),7.39 (d, 1H), 7.26 (t, 1H), 7.12 (d, 1H), 6.96 (t, 1H).

Step 3: Synthesis of5-nitro-2-[2-[4-(trifluoromethyl)pyrazol-1-yl]phenoxy]pyridine (A14)

To a stirred solution of 2-[4-(trifluoromethyl)pyrazol-1-yl]phenol (0.20g, 0.88 mmol) in DMF (5 mL) was added K₂CO₃ (0.242 g, 1.75 mmol) and2-chloro-5-nitro-pyridine (0.166 mg, 1.05 mmol). The reaction was heatedat 80° C. for 3 hours, allowed to cool to RT, diluted with H₂O andextracted with Et₂O (×3). The combined organic extracts were washed withbrine, dried over MgSO₄ and evaporated to dryness under reduced pressureto give a brown solid. The crude product was purified by flashchromatography on silica gel using a gradient of 5-50% EtOAc inisohexane as eluent to give the desired product (0.078 g, 26%) as a paleyellow solid.

¹H NMR (400 MHz, CDCl₃) δ 8.91 (s, 1H), 8.45 (dd, 1H), 8.02 (s, 1H),7.79-7.70 (m, 2H), 7.55-7.49 (m, 1H), 7.49-7.42 (m, 1H), 7.32 (d, 1H),7.03 (d, 1H)

EXAMPLE 5: SYNTHESIS OF5-CHLORO-2-[2-(4-CHLOROPYRAZOL-1-YL)PHENOXY]-3-FLUORO-PYRIDINE (A24)Step 1: Synthesis of 5-chloro-3-fluoro-2-(2-iodophenoxy)pyridine

To a stirred solution of 2-iodo phenol (6.40 g, 29.1 mmol) in DMF (64mL) was added K₂CO₃ (8.04 g, 58.2 mmol) and 5-chloro,2,3-difluoropyridine (5.22 g, 34.9 mmol) and the reaction heated at 80°C. for 16 hours. The reaction was cooled to RT, diluted with H₂O (200mL) and extracted with Et₂O (3×75 ml_). The combined organic extractswere washed with brine, dried over MgSO₄ and evaporated to dryness underreduced pressure to give a yellow oil. The crude product was purified byflash chromatography on silica gel using a gradient of 5-50% EtOAc incyclohexane to give the desired product (10.10 g, 99%) as a colourlessoil.

¹H NMR (400 MHz, CDCl₃) δ 7.91-7.82 (m, 2H), 7.53 (dd, 1H), 7.41 (t,1H), 7.18 (d, 1H), 7.01 (t, 1H)

Step 2: Synthesis of5-chloro-2-[2-(4-chloropyrazol-1-yl)phenoxy]-3-fluoro-pyridine (A24)

To a stirred solution of 5-chloro-3-fluoro-2-(2-iodophenoxy)pyridine(0.20 g, 0.572 mmol), in 1,4-dioxane (4 mL) was added4-chloro-1H-pyrazole (0.117 mg, 1.14 mmol), CuI (0.109 g, 0.572 mmol),N,N′-dimethylethane-1,2-diamine (0.108 g, 1.14 mmol) and K₂CO₃ (0.168 g,1.22 mmol) and the reaction heated at reflux for 16 hours. The reactionwas allowed to cool to RT, diluted with H₂O (10 mL) and extracted withEtOAc (3×15 mL). The combined organic extracts were washed with brine,dried over MgSO₄ and evaporated to dryness under reduced pressure togive a brown oil. The crude product was purified by flash chromatographyon silica gel using a gradient of 5-50% EtOAc in cyclohexane as eluentto give the desired product (27 mg, 14%) as a white solid.

¹H NMR (400 MHz, CDCl₃) δ 7.81 (s, 1H), 7.72 (d, 1H), 7.69 (dd, 1H),7.48 (s, 1H), 7.42 (dd, 1H), 7.37-7.28 (m, 2H), 7.19 (dd, 1H).

EXAMPLE 6: SYNTHESIS OF3-[2-[(5-CHLORO-3-FLUORO-2-PYRIDYL)OXY]-6-FLUORO-PHENYL]-5-(TRIFLUOROMETHYL)ISOXAZOLE(A25) Step 1: Synthesis of3-fluoro-2-[5-(trifluoromethyl)isoxazol-3-yl]phenol

To a stirred solution of3-(2-fluoro-6-hydroxy-phenyl)-5-(trifluoromethyl)-4H-isoxazol-5-ol (20.0g, 75.4 mmol) in toluene (150 mL) was added p-toluene sulphonic acidmonohydrate (1.59 g, 9.05 mmol). The reaction was heated at reflux for 2h with azeotropic removal of water then cooled to RT and evaporated todryness under reduced pressure. The residue was dissolved in CH₂Cl₂ (500ml) and added gradually to a stirred solution of saturated aq. NaHCO₃(200 ml). The organic phase was separated and washed with H₂O then brineand evaporated to dryness under reduced pressure to leave the desiredproduct (17.41 g, 93%) as an off white solid which was used withoutfurther purification.

¹H NMR (400 MHz, CDCl₃) δ 9.54 (s, 1H), 7.35 (m, 2H), 6.94 (d, 1H), 6.76(t, 1H).

Step 2: Synthesis of3-[2-[(5-chloro-3-fluoro-2-pyridyl)oxy]-6-fluoro-phenyl]-5-(trifluoromethyl)isoxazole(A25)

To a solution of 3-fluoro-2-[5-(trifluoromethyl)isoxazol-3-yl]phenol(1.00 g, 4.05 mmol) in N,N-dimethylformamide (15 mL) was added5-chloro-2,3-difluoro-pyridine (3.03 g, 20.2 mmol) and potassiumcarbonate (0.85 g, 6.07 mmol). The reaction was heated at 80° C. for 3.5hours, allowed to cool to RT and then quenched by addition of H₂O. Thereaction was then extracted with EtOAc (×3) and the combined organicextracts washed with H₂O and brine before being dried over MgSO₄, andevaporated to dryness under reduced pressure to leave a yellow oil. Thecrude product was purified by flash chromatography on silica gel using agradient of 100% cyclohexane to 10% EtOAc/cyclohexane as eluent to givethe desired product (30 mg, 2%) as a pale yellow gum.

¹H NMR (400 MHz, CDCl₃) δ 7.81 (s, 1H), 7.54 (m, 2H), 7.15 (t, 1H), 7.10(d, 1H), 6.99 (s, 1H)

EXAMPLE 7: SYNTHESIS OF5-CHLORO-3-FLUORO-2-(2-IMIDAZOL-1-YLPHENOXY)PYRIDINE (A28) Step 1:Synthesis of 1-(2-methoxyphenyl)imidazole

A mixture of imidazole (0.806 g, 0.012 mol), (2-methoxyphenyl)boronicacid (1.50 g, 0.0099 mol) and Cu(I)Cl (0.100 g, 0.001 mol) in MeOH (50mL) was heated at reflux overnight. The reaction mixture was allowed tocool to RT and evaporated to dryness under reduced pressure. The crudeproduct was purified by flash chromatography on silica gel using agradient of 0-5% MeOH/DCM as eluent to give the desired product (133 mg,7%) as a brown oil.

¹H NMR (400 MHz, CDCl₃) δ 7.79 (s, 1H), 7.34 (t, 1H), 7.28 (d, 1H), 7.20(s, 1H), 7.16 (s, 1H), 7.09-7.00 (m, 2H), 3.84 (s, 3H)

Step 2: Synthesis of 2-imidazol-1-ylphenol

To a solution of 1-(2-methoxyphenyl)imidazole (55 mg, 0.89 mmol) indichloromethane (18 mL) at 0° C., under nitrogen, was added dropwiseboron tribromide (1M solution in DCM) (2.22 mL, 2.22 mmol) maintainingtemperature at <5° C. Once addition was complete, the reaction mixturewas allowed to stir at this temperature for 1 hour and then allowed towarm to RT and stirred at RT for 72 hours. The reaction mixture wasquenched with water and adjusted to pH 7 with saturated aqueous sodiumbicarbonate solution then washed with DCM (×3). An off-white solidprecipitated out of the aqueous layer. The solid was filtered off,washed with a little water and dried in a vacuum oven at 40° C. for 3hours to give the desired product (133 mg, 93%) as a beige solid.

¹H NMR (400 MHz, CD₃OD) δ=7.92 (s, 1H), 7.38 (s, 1H), 7.30 (d, 1H), 7.22(t, 1H), 7.09 (s, 1H), 7.01 (d, 1H), 6.93 (t, 1H)

Step 3: Synthesis of5-chloro-3-fluoro-2-(2-imidazol-1-ylphenoxy)pyridine (A28)

A mixture of 5-chloro-2,3-difluoro-pyridine (0.149 g, 0.10 mmol),2-imidazol-1-ylphenol (0.133 g, 0.83 mmol) and K₂CO₃ (0.230 g, 1.66mmol) in DMF (5 mL) was heated at 90° C. overnight. The reaction mixturewas allowed to cool to RT, diluted with water and extracted with EtOAc(×3). The combined organic extracts were washed with brine, dried overMgSO₄ and evaporated to dryness under reduced pressure. The crudeproduct was purified by flash chromatography on silica gel using agradient of 0-5% MeOH in DCM as eluent to give the desired product(0.226 g, 94%) as a yellow oil.

¹H NMR (400 MHz, CDCl₃) δ 7.71 (s, 1H), 7.68 (s, 1H), 7.51-7.34 (m, 4H),7.31 (d, 1H), 7.14 (s, 1H), 7.03 (s, 1H)

EXAMPLE 8: SYNTHESIS OF3-[(5-CHLORO-3-FLUORO-2-PYRIDYL)OXY]-2-[4-(TRIFLUOROMETHYL)PYRAZOL-1-YL]BENZONITRILE(A33) Step 1: Synthesis of3-hydroxy-2-[4-(trifluoromethyl)pyrazol-1-yl]benzonitrile

To a solution of 2-fluoro-3-hydroxy-benzonitrile (1.0 g, 7.3 mmol) and4-(trifluoromethyl)-1H-pyrazole (1.1 g, 8.0 mmol) inN,N-dimethylacetamide (15 mL) under a nitrogen atmosphere was addedpowdered K₂CO₃ (3.1 g, 22 mmol). The resultant mixture was heated at150° C. for 22 hours. The reaction mixture was allowed to cool to RT,diluted with water and extracted with EtOAc (×4). The combined organicextracts were washed with brine, dried over MgSO₄ and evaporated todryness to give an orange liquid. The crude product was purified byflash chromatography on silica gel using a gradient of 20 to 40% EtOAcin cyclohexane as eluent to give the desired product (594 mg, 32%) as ayellow solid.

¹H NMR (400 MHz, CDCl₃) δ=8.64 (s, 1H), 8.07 (s, 1H), 7.42-7.35 (m, 3H).

Step 2: Synthesis of3-[(5-chloro-3-fluoro-2-pyridyl)oxy]-2-[4-(trifluoromethyl)pyrazol-1-yl]benzonitrile(A33)

To a solution of3-hydroxy-2-[4-(trifluoromethyl)pyrazol-1-yl]benzonitrile (0.180 g,0.711 mmol) and 5-chloro-2,3-difluoro-pyridine (0.138 g, 0.924 mmol) inN,N-dimethylformamide (4.50 mL) was added K₂CO₃ (0.248 g, 1.78 mmol).The mixture was heated under microwave irradiation at 130° C. for 1hour. The reaction mixture was poured into water and extracted withEtOAc (×3). The combined organic extracts were washed with 1M NaOHsolution then brine, dried over MgSO₄ and evaporated to dryness underreduced pressure to give a brown liquid. The crude product was purifiedby flash chromatography on silica gel using a gradient of 0 to 50% EtOAcin cyclohexane as eluent to give the desired product (0.191 g, 63%) as awhite solid.

¹H NMR (400 MHz, CDCl₃) δ=8.03 (s, 1H), 7.87 (s, 1H), 7.78 (d, 1H), 7.75(dd, 1H), 7.64 (d, 1H), 7.63 (s, 1H), 7.48 (dd, 1H)

EXAMPLE 9: SYNTHESIS OF5-CHLORO-3-FLUORO-2-[3-METHOXY-2-[4-(TRIFLUOROMETHYL)PYRAZOL-1-YL]PHENOXY]PYRIDINE(A36) Step 1: Synthesis of1-(2-methoxyphenyl)-4-(trifluoromethyl)pyrazole

A solution of 4-(trifluoromethyl)-1H-pyrazole (291 mg, 2.14 mmol),1-bromo-2-methoxy-benzene (200 mg, 1.07 mmol), Cu(I)I (204 mg, 1.07mmol), N,N′-dimethylethane-1,2-diamine (188 mg, 2.14 mmol) and K₂CO₃(227 mg, 2.25 mmol) in 1,4-dioxane (20 mL) was heated at reflux for 18hours. The reaction was allowed to cool to RT and evaporated to drynessunder reduced pressure. The crude product was purified by flashchromatography on silica gel using a gradient of 5-50% EtOAc incyclohexane as eluent to give the desired product (169 mg, 65%) as acolourless oil.

¹H NMR (400 MHz, CDCl₃) δ=8.31 (s, 1H), 7.88 (s, 1H), 7.72 (d, 1H), 7.36(t, 1H), 7.11-7.03 (m, 2H), 3.91 (s, 3H).

Step 2: Synthesis of[3-methoxy-2-[4-(trifluoromethyl)pyrazol-1-yl]phenyl]acetate

A solution of 1-(2-methoxyphenyl)-4-(trifluoromethyl)pyrazole (326 mg,1.35 mmol), Pd(OAc)₂ (31 mg, 0.13 mmol) and (diacetoxyiodo)benzene (1.77g, 5.38 mmol) in acetic acid (13.5 mL) was heated at 100° C. for 2hours. The reaction was allowed to cool to RT, then evaporated todryness under reduced pressure and azeotroped three times with toluene.The crude product was purified by flash chromatography on silica gelusing a gradient of 5-100% EtOAc in cyclohexane as eluent to give thedesired product (292 mg, 72%) as a yellow solid.

¹H NMR (400 MHz, CDCl₃) δ=7.90 (s, 1H), 7.81 (s, 1H), 7.46 (t, 1H), 6.95(d, 1H), 6.85 (d, 1H), 3.83 (s, 3H), 2.08 (s, 3H)

Step 3: Synthesis of 3-methoxy-2-[4-(trifluoromethyl)pyrazol-1-yl]phenol

A solution of[3-methoxy-2-[4-(trifluoromethyl)pyrazol-1-yl]phenyl]acetate (295 mg,0.95 mmol) and NaOH (133 mg, 3.32 mmol) in MeOH (5.7 mL) and H₂O (0.57mL) was stirred at RT overnight. The reaction was diluted with water,made acidic with 2M HCl and extracted with DCM (×3). The combinedorganic extracts were washed with brine, dried over MgSO₄ and evaporatedto dryness under reduced pressure to give the desired product (245 mg,quant) which was used without further purification.

¹H NMR (400 MHz, CDCl₃) δ=10.1 (br, 1H), 8.52 (s, 1H), 7.91 (s, 1H),7.17 (t, 1H), 6.74 (d, 1H), 6.59 (d, 1H), 3.91 (s, 3H)

Step 4: Synthesis of5-chloro-3-fluoro-2-[3-methoxy-2-[4-(trifluoromethyl)pyrazol-1-yl]phenoxy]pyridine(A36)

A solution of 3-methoxy-2-[4-(trifluoromethyl)pyrazol-1-yl]phenol (150mg, 0.58 mmol), 5-chloro-2,3-difluoro-pyridine (104 mg, 0.70 mmol) andK₂CO₃ (161 mg, 1.16 mmol) in DMF (2 mL) was heated at 80° C. for 18hours. The reaction was allowed to cool to RT, diluted with water andextracted with EtOAc (×3). The combined organic extracts were washedwith brine, dried over MgSO₄ and evaporated to dryness under reducedpressure. The crude product was purified by flash chromatography onsilica gel using a gradient of 5-30% EtOAc in cyclohexane as eluent togive the desired product (169 mg, 75%) as a colourless gum.

¹H NMR (400 MHz, CDCl₃) δ=7.78 (s, 1H), 7.72 (s, 2H), 7.47 (t, 1H), 7.39(dd, 1H), 7.00-6.91 (m, 2H), 3.83 (s, 3H)

EXAMPLE 10: SYNTHESIS OF5-CHLORO-3-FLUORO-2-[3-IODO-2-[4-(TRIFLUOROMETHYL)PYRAZOL-1-YL]PHENOXY]PYRIDINE(A57) Step 1: Synthesis of1-(2-iodo-6-methoxy-phenyl)-4-(trifluoromethyl)pyrazole

A solution of 1-(2-methoxyphenyl)-4-(trifluoromethyl)pyrazole (270 mg,1.11 mmol), Pd(OAc)₂ (26 mg, 0.11 mmol) and N-iodosuccinimide (284 mg,1.23 mmol) in acetic acid (11.5 mL) was heated at 100° C. for 2 hours.The reaction was allowed to cool to RT, then evaporated to dryness underreduced pressure and azeotroped three times with toluene. The crudeproduct was purified by flash chromatography on silica gel using agradient of 5-30% EtOAc in cyclohexane as eluent to give the desiredproduct (397 mg, 97%) as a pale yellow gum.

¹H NMR (400 MHz, CDCl₃) δ=7.95 (s, 1H), 7.75 (s, 1H), 7.52 (d, 1H), 7.16(t, 1H), 7.00 (d, 1H), 3.77 (s, 3H)

Step 2: Synthesis of 3-iodo-2-[4-(trifluoromethyl)pyrazol-1-yl]phenol

To a solution of 1-(2-iodo-6-methoxy-phenyl)-4-(trifluoromethyl)pyrazole(234 mg, 0.64 mmol) in dichloromethane (12.5 mL) under an atmosphere ofnitrogen was added BBr₃ (1M solution in DCM) (1.59 mL, 1.59 mmol)dropwise. The reaction mixture was stirred at RT for 2.5 hours, thenquenched with water. The reaction was basified with saturated aqueoussodium bicarbonate solution and extracted with DCM (×3). The combinedorganic extracts were washed with brine, dried over MgSO₄ and evaporatedto dryness under reduced pressure to give the desired product (228 mg,quant) as a beige solid which was used without further purification.

¹H NMR (400 MHz, CDCl₃) δ=8.20 (s, 1H), 8.02 (s, 1H), 7.51 (d, 1H),7.11-7.01 (m, 2H)

Step 3: Synthesis of5-chloro-3-fluoro-2-[3-iodo-2-[4-(trifluoromethyl)pyrazol-1-yl]phenoxy]pyridine(A57)

A solution of 3-iodo-2-[4-(trifluoromethyl)pyrazol-1-yl]phenol (228 mg,0.64 mmol), 5-chloro-2,3-difluoro-pyridine (116 mg, 0.77 mmol) and K₂CO₃(178 mg, 1.29 mmol) in DMF (2 mL) was heated at 80° C. for 18 hours. Thereaction was allowed to cool to RT, diluted with water and extractedwith EtOAc (×3). The combined organic extracts were washed with brine,dried over MgSO₄ and evaporated to dryness under reduced pressure. Thecrude product was purified by flash chromatography on silica gel using agradient of 5-30% EtOAc in cyclohexane as eluent to give the desiredproduct (210 mg, 67%) as a white solid.

¹H NMR (400 MHz, CDCl₃ δ=7.88 (dd, 1H), 7.80 (dd, 2H), 7.72 (s, 1H),7.40 (dd, 1H), 7.36-7.22 (m, 2H)

EXAMPLE 11: SYNTHESIS OF5-CHLORO-2-[2-(5-CHLORO-2-THIENYL)PHENOXY]-3-FLUORO-PYRIDINE (A66) Step1: Synthesis of 2-chloro-5-(2-methoxyphenyl)thiophene

A degassed solution of 1-iodo-2-methoxy-benzene (500 mg, 2.14 mmol),(5-chloro-2-thienyl)boronic acid (416 mg, 2.56 mmol), Pd(OAc)₂ (25 mg,0.11 mmol), 2-Dicyclohexylphosphino-2′-methylbiphenyl (MePhos) (159 mg,0.43 mmol) and KF (372 mg, 6.41 mmol) in 1,4-dioxane (7.5 mL) under anN₂ atmosphere was heated at reflux for 18 hours. The reaction wasallowed to cool to RT, diluted with water and extracted with EtOAc (×3).The combined organic extracts were washed with brine, dried over MgSO₄and evaporated to dryness under reduced pressure. The crude product waspurified by flash chromatography on silica gel using a gradient of 5-15%EtOAc in cyclohexane as eluent to give the desired product (438 mg, 91%)as an orange oil.

¹H NMR (400 MHz, CDCl₃ δ=7.58 (d, 1H), 7.28-7.20 (m, 2H), 7.02-6.92 (m,2H), 6.88 (d, 1H), 3.92 (s, 3H)

Step 2: Synthesis of 2-(5-chloro-2-thienyl)phenol

To a solution of 2-chloro-5-(2-methoxyphenyl)thiophene (438 mg, 1.95mmol) in DCM (39 mL) at room temperature and under an N₂ atmosphere wasadded dropwise BBr₃ (1M solution in DCM) (4.87 mL, 4.87 mmol). Thereaction mixture was stirred for 3 hours and then was quenched withwater, made basic with saturated aqueous sodium bicarbonate andextracted with EtOAc (×3). The combined organic extracts were washedwith brine, dried over MgSO₄ and evaporated to dryness under reducedpressure to give an orange solid (559 mg) which was used without furtherpurification.

Step 3: Synthesis of5-chloro-2-[2-(5-chloro-2-thienyl)phenoxy]-3-fluoro-pyridine (A66)

A stirred solution of the crude 2-(5-chloro-2-thienyl)phenol from step 2above (559 mg), 5-chloro-2,3-difluoro-pyridine (476 mg, 3.18 mmol) andK₂CO₃ (733 mg, 5.31 mmol) in DMF (5 mL) was heated at 80° C. for 18hours. The reaction was allowed to cool to RT, diluted with water andextracted with EtOAc (×3). The combined organic extracts were washedwith brine, dried over MgSO₄ and evaporated to dryness under reducedpressure. The crude product was purified by flash chromatography onsilica gel first using a gradient of 5-25% EtOAc in cyclohexane aseluent and secondly using a gradient of 0-10% EtOAc in cyclohexane togive the desired product (51 mg) as an orange gum.

¹H NMR (400 MHz, CDCl₃) δ=7.81 (s, 1H), 7.62 (d, 1H), 7.51 (d, 1H),7.40-7.22 (m, 2H), 7.19-7.11 (m, 2H), 6.82 (s, 1H)

EXAMPLE 12: SYNTHESIS OF5-CHLORO-3-FLUORO-2-[2-[4-(TRIFLUOROMETHYL)-2-THIENYL]PHENOXY]PYRIDINE(A97) Step 1: Synthesis of2-(2-methoxyphenyl)-4-(trifluoromethyl)thiophene

A degassed solution of 3-(trifluoromethyl)thiophene (0.56 g, 3.68 mmol),1-bromo-2-methoxybenzene (0.688 g, 3.68 mmol), K₂CO₃ (0.771 g, 5.52mmol), Pd(OAc)₂ (17 mg, 0.076 mmol), pivalic acid (0.128 mL, 1.10 mmol)and tricyclohexylphosphine tetrafluoroborate (54 mg, 0.147 mmol) inN,N-dimethylacetamide (12 mL) was heated at 100° C. under an atmosphereof N₂ for 18 hours. The reaction was allowed to cool to RT, diluted withwater and extracted with EtOAc (×3). The combined organic extracts werewashed with brine, dried over MgSO₄ and evaporated to dryness underreduced pressure. The crude product was purified twice by flashchromatography on silica gel both times using a gradient of 0-5% EtOAcin cyclohexane to give the desired product (210 mg, 22%) as a paleyellow oil.

¹H NMR (400 MHz, CDCl₃) δ 7.69-7.61 (m, 2H), 7.58 (s, 1H), 7.30 (t, 1H),7.04-6.97 (m, 2H), 3.94 (s, 3H)

Step 2: Synthesis of 2-[4-(trifluoromethyl)-2-thienyl]phenol

To a solution of 2-(2-methoxyphenyl)-4-(trifluoromethyl)thiophene (210mg, 0.81 mmol) in DMF (2.5 mL) under an atmosphere of N₂ were added1-dodecanethiol (0.397 mL, 1.626 mmol) and lithium t-butoxide (1M inTHF) (1.6 mL, 1.6 mmol). The reaction mixture was heated at 100° C. for18 hours. The reaction mixture was allowed to cool to room temperature,diluted with water and extracted with EtOAc (×3). The combined organicextracts were washed with brine, dried over MgSO₄ and evaporated todryness under reduced pressure. The crude product was purified by flashchromatography on silica gel using a gradient of 0-20% EtOAc incyclohexane as eluent to give the desired product (189 mg, 95%) as ayellow oil.

¹H NMR (400 MHz, CDCl₃) δ=7.71 (s, 1H), 7.52 (s, 1H), 7.48 (d, 1H),7.29-7.20 (m, 1H), 6.97 (t, 1H), 6.91 (d, 1H), 5.34 (s, 1H)

Step 3: Synthesis of5-chloro-3-fluoro-2-[2-[4-(trifluoromethyl)-2-thienyl]phenoxy]pyridine(A97)

A solution of 2-[4-(trifluoromethyl)-2-thienyl]phenol (174 mg, 0.71mmol), 5-chloro-2,3-difluoro-pyridine (128 mg, 0.86 mmol) and K₂CO₃ (197mg, 1.43 mmol) in DMF (5 mL) was heated at 140° C. for 30 minutes undermicrowave irradiation. The reaction was allowed to cool to RT, dilutedwith water and extracted with EtOAc (×3). The combined organic extractswere washed with brine, dried over MgSO₄ and evaporated to dryness underreduced pressure. The crude product was purified by flash chromatographytwice on silica gel first using a gradient of 0-5% EtOAc in cyclohexaneas eluent followed by a gradient of 0-30% DCM in cyclohexane as eluentto give the desired product (136 mg, 51%) as a colourless gum.

¹H NMR (400 MHz, CDCl₃) δ=7.80 (s, 1H), 7.69 (d, 1H), 7.61 (s, 1H),7.52-7.48 (m, 2H), 7.40 (t, 1H), 7.31 (t, 1H), 7.20 (d, 1H)

EXAMPLE 13: SYNTHESIS OF2-[2-[3,5-BIS(TRIFLUOROMETHYL)PYRAZOL-1-YL]PHENOXY]-5-CHLORO-3-FLUORO-PYRIDINE(A123) Step 1: Synthesis of1-(2-methoxyphenyl)-3,5-bis(trifluoromethyl)pyrazole

A solution of (2-methoxyphenyl)hydrazine hydrochloride (500 mg, 2.86mmol) and 1,1,1,5,5,5-hexafluoropentane-2,4-dione (596 mg, 2.86 mmol) inEtOH (3.6 mL) and cone. H₂SO₄ (0.1 mL) was heated at reflux for 18hours. The reaction was allowed to cool to RT, diluted with water andextracted with EtOAc (×3). The combined organic extracts were washedwith brine, dried over MgSO₄ and evaporated to dryness under reducedpressure. The crude product was purified by flash chromatography onsilica gel using a gradient of 0-50% EtOAc in cyclohexane as gradient togive the desired product (101 mg, 11%) as a yellow oil.

¹H NMR (400 MHz, CDCl₃ δ=7.52 (t, 1H), 7.34 (d, 1H), 7.09-7.00 (m, 3H),3.79 (s, 3H)

Step 2: Synthesis of 2-[3,5-bis(trifluoromethyl)pyrazol-1-yl]phenol

To a stirred solution of1-(2-methoxyphenyl)-3,5-bis(trifluoromethyl)pyrazole (101 mg, 0.33 mmol)in dichloromethane (6.5 mL) under an N₂ atmosphere was added borontribromide (1M solution in DCM) (0.81 mL, 0.81 mmol) dropwise. Thereaction was stirred at RT overnight. The reaction mixture was quenchedwith water and extracted with DCM (×3). The combined organic extractswere washed with brine, dried over MgSO₄ and evaporated to dryness underreduced pressure to give the desired product (91 mg, 94%) as a yellowgum, which was used without further purification.

¹H NMR (400 MHz, CDCl₃) δ=7.45-7.30 (m, 2H), 7.18-7.07 (m, 2H), 7.02 (t,1H), 6.32 (s, 1H)

Step 3: Synthesis of2-[2-[3,5-bis(trifluoromethyl)pyrazol-1-yl]phenoxy]-5-chloro-3-fluoro-pyridine(A123)

A solution of 2-[3,5-bis(trifluoromethyl)pyrazol-1-yl]phenol (97 mg,0.23 mmol), 5-chloro-2,3-difluoro-pyridine (55 mg, 0.35 mmol) and K₂CO₃(85 mg, 0.61 mmol) in DMF (5 mL) was heated at 140° C. under microwaveirradiation for 30 minutes. The reaction was allowed to cool to RT,diluted with water and extracted with EtOAc (×3). The combined organicextracts were washed with brine, dried over MgSO₄ and evaporated todryness under reduced pressure. The crude product was purified by flashchromatography on silica gel using a gradient of 0-10% EtOAc incyclohexane as eluent to give the desired product (97 mg, 75%) as abrown gum.

¹H NMR (400 MHz, CDCl₃ δ=7.84 (s, 1H), 7.61 (t, 1H), 7.52 (d, 1H), 7.45(d, 1H), 7.43-7.35 (m, 2H), 6.96 (s, 1H)

EXAMPLE 14: SYNTHESIS OF2-[2-[(5-CHLORO-3-FLUORO-2-PYRIDYL)OXY]PHENYL]THIAZOLE (A147) Step 1:Synthesis of 2-thiazol-2-ylphenol

A degassed solution of 2-chlorothiazole (260 mg, 2.18 mmol),(2-hydroxyphenyl)boronic acid (250 mg, 1.81 mmol), Na₂C₀₃ (576 mg, 5.44mmol), tetrakis(triphenylphosphine)palladium (21 mg, 0.018 mmol) intoluene (2.5 ml_), EtOH (2.5 mL) and water (1.25 mL) was heated at 160°C. for 30 minutes under microwave irradiation. The reaction was allowedto cool to RT, diluted with water and extracted with EtOAc (×3). Thecombined organic extracts were washed with brine, dried over MgSO₄ andevaporated to dryness under reduced pressure. The crude product waspurified by flash chromatography on silica gel using a gradient of 0-50%EtOAc in cyclohexane as eluent to give the desired product (127 mg, 40%)as a pale green oil.

¹H NMR (400 MHz, CDCl₃) δ=12.3 (s, 1H), 7.79 (s, 1H), 7.63 (d, 1H),7.35-7.21 (m, 2H), 7.05 (d, 1H), 6.90 (t, 1H)

Step 2: Synthesis of2-[2-[(5-chloro-3-fluoro-2-pyridyl)oxy]phenyl]thiazole (A147)

A solution of 2-thiazol-2-ylphenol (127 mg, 0.72 mmol),5-chloro-2,3-difluoro-pyridine (129 mg, 0.86 mmol) and K₂CO₃ (198 mg,1.43 mmol) in DMF (5 mL) was heated at 140° C. for 30 minutes undermicrowave irradiation. The reaction was allowed to cool to RT, dilutedwith water and extracted with EtOAc (×3). The combined organic extractswere washed with brine, dried over MgSO₄ and evaporated to dryness underreduced pressure. The crude product was purified by flash chromatographyon silica gel using a gradient of 0-20% EtOAc in cyclohexane as eluentto give the desired product (208 mg, 95%) as a pale yellow oil.

¹H NMR (400 MHz, CDCl₃) δ=8.42 (d, 1H), 7.88 (s, 1H), 7.73 (s, 1H), 7.55(d, 1H), 7.46 (t, 1H), 7.41-7.32 (m, 2H), 7.21 (d, 1H)

TABLE 1 Examples of herbicidal compounds of the present invention.

¹H NMR (400 Com- MHz, CDCl₃ pound n R¹ Q m R² unless stated) A1 1 3-F5-(3- 2 3-F, 7.83 (d, 1H), 7.57 difluoro- 5-Cl (d, 2H), 7.24-7.08methyl)- (m, 2H), 6.94-6.61 isoxazole (m, 2H) A2 1 3-F 5-(3- 1 5-NO₂8.95 (d, 1H), 8.64- difluoro- 8.43 (m, 1H), 7.59 methyl)- (dt, 1H),7.32-7.10 isoxazole (m, 3H), 6.97-6.53 (m, 2H) A3 1 3-F 2-(5- 2 3-F,7.78 (d, 1H), 7.67- trifluoro- 5-Cl 7.42 (m, 3H), 7.24- methyl)- 7.05(m, 2H) oxazole A4 1 3-F 5-(3- 2 3-Cl, 8.07-7.40 (m, 3H), difluoro- 5-Cl7.23-7.02 (m, 2H), methyl)- 7.00-6.51 (m, 2H) isoxazole A5 1 3-F 5-(3- 16-Cl 7.75-7.61 (m, 1H), difluoro- 7.55-7.45 (m, 1H), methyl)- 7.21-7.00(m, 3H), isoxazole 6.95-6.56 (m, 3H) A6 1 3-F 5-(3- 1 5-CF₃ 8.35 (s,1H), 7.94 difluoro- (d, 1H), 7.60-7.50 methyl)- (m, 1H), 7.23-6.99isoxazole (m, 3H), 6.80 (s, 1H), 6.75 (t, 1H) A7 1 3-F 5-(3- 1 6-F7.85-7.77 (m, 1H), difluoro- 7.55-7.47 (m, 1H), methyl)- 7.21-7.02 (m,2H), isoxazole 6.95-6.57 (m, 4H) A8 1 3-F 5-(3- 1 4-CF₃ 8.24 (d, 1H),7.58- difluoro- 7.50 (m, 1H), 7.26- methyl)- 7.05 (m, 4H), 6.80isoxazole (s, 1H), 6.75 (t, 1H) A9 1 3-F 5-(3- 1 5-Cl 8.03 (d, 1H),7.73- difluoro- 7.62 (m, 1H), 7.57- methyl)- 7.43 (m, 1H), 7.19-isoxazole 7.09 (m, 1H), 7.09- 7.03 (m, 1H), 6.99 (d, 1H), 6.80 (d 1H),6.75 (t, 1H) A10 1 3-F 5-(3- 2 3-F, 7.76 (d, 1H), 7.53- difluoro- 5-F7.48 (m, 1H), 7.41- methyl)- 7.31 (m, 1H), 7.22- isoxazole 6.98 (m, 2H),6.88 (d, 1H), 6.75 (t, 1H) A11 1 3-F 5-(3- 2 4-Cl, 7.54-7.49 (m, 1H),difluoro- 6-Cl 7.22-7.12 (m, 1H), methyl)- 7.10-7.05 (m, 2H), isoxazole6.95 (s, 1H), 6.82 (d, 1H), 6.78 (t, 1H) A12 1 3-F 5-(3- 1 5-CN 8.36 (d,1H), 7.97 difluoro- (dd, 1H), 7.59- methyl)- 7.51 (m, 1H), 7.29-isoxazole 7.06 (m, 3H), 6.81 (d, 1H), 6.75 (t, 1H) A13 1 3-F 5-(3- 23-F, 7.96 (s, 1H), 7.55- difluoro- 4-Cl 7.48 (m, 1H), 7.19- methyl)-7.00 (m, 3H), 6.81 isoxazole (d, 1H), 6.78 (t, 1H) A14 0 — 4- 1 5-NO₂8.91 (s, 1H), 8.45 (trifluoro- (dd, 1H), 8.02 (s, methyl)- 1H),7.79-7.70 (m, pyrazol- 2H), 7.55-7.49 (m, 1-yl 1H), 7.49-7.42 (m, 1H),7.32 (d, 1H), 7.03 (d, 1H) A15 0 — 4- 1 5-CF₃ 8.32 (s, 1H), 8.03(trifluoro- (s, 1H), 7.89 (dd, methyl)- 1H), 7.79-7.71 (m, pyrazol- 2H),7.52-7.46 (m, 1-yl 1H), 7.46-7.38 (m, 1H), 7.30 (d, 1H), 7.01 (d, 1H)A16 0 — 4- 2 3-F, 8.18 (s, 1H), 7.81- (trifluoro- 5-Cl 7.73 (m, 3H),7.51- methyl)- 7.43 (m, 2H), 7.40 pyrazol- (t, 1H), 7.32 (d, 1-yl 1H)A17 0 — 4- 1 5-Cl 8.09 (s, 1H), 8.02 (trifluoro- (d, 1H), 7.80 (s,methyl)- 1H), 7.76 (dd, pyrazol- 1H), 7.62 (dd, 1-yl 1H), 7.49-7.41 (m,1H), 7.41-7.33 (m, 1H), 7.25 (d, 1H), 6.88 (d, 1H) A18 0 — 4- 2 3-F,8.20 (s, 1H), 7.81- (trifluoro- 5-F 7.73 (m, 2H), 7.72 methyl)- (s, 1H),7.49-7.42 pyrazol- (m, 1H), 7.41-7.34 1-yl (m, 1H), 7.34-7.22 (m, 2H)A19 0 — 4- 1 5-CN 8.34 (s, 1H), 8.01 (trifluoro- (s, 1H), 7.90 (dd,methyl)- 1H), 7.79-7.70 (m, pyrazol- 2H), 7.55-7.48 (m, 1-yl 1H),7.48-7.41 (m, 1H), 7.31 (d, 1H), 7.01 (d, 1H) A20 1 3-F 5-(3- 2 3-F,7.90 (d, 1H), 7.66 difluoro- 5-Br (dd, 1H), 7.52 (dt, methyl)- 1H), 7.17(ddd, isoxazole 1H), 7.10 (td, 1H), 6.95-6.57 (m, 2H) A21 1 3-F 5-(3- 23-F, 8.11 (dd, 1H), difluoro- 5-CF₃ 7.73 (dd, 1H), methyl)- 7.56 (dt,1H), isoxazole 7.26-7.18 (m, 1H), 7.16 (td, 1H), 6.92-6.57 (m, 2H) A22 13-F 5-(3- 2 3-F, 8.73 (d, 1H), 8.32 difluoro- 5-NO₂ (dd, 1H), 7.60 (dt,methyl)- 1H), 7.30-7.22 (m, isoxazole 1H), 7.18 (td, 1H), 6.94-6.56 (m,2H) A23 1 3-F 5-(3- 2 3-F, 8.08 (d, 1H), 7.79 difluoro- 5-CN (dd, 1H),7.57 (dt, methyl)- 1H), 7.23 (ddd, isoxazole 1H), 7.15 (td, 1H),6.97-6.58 (m, 2H) A24 0 — 4- 2 3-F, 7.81 (s, 1H), 7.72 (chloro) 5-Cl (d,1H), 7.69 (dd, pyrazol- 1H), 7.48 (s, 1H), 1-yl 7.42 (dd, 1H), 7.37-7.28(m, 2H), 7.19 (dd, 1H) A25 1 3-F 3-(5- 2 3-F, 7.81 (s, 1H), 7.54trifluoro- 5-Cl (m, 2H), 7.15 (t, methyl)- 1H), 7.10 (d, 1H), isoxazole6.99 (s, 1H) A26 0 — 4-cyano- 2 3-F, 8.32 (s, 1H), 7.91 pyrazol- 5-Cl(s, 1H), 7.82 (d, 1-yl 1H), 7.79 (dd, 1H), 7.53 (dd, 1H), 7.51-7.45 (m,1H), 7.45-7.39 (m, 1H), 7.30 (dd, 1H) A27 0 — 4-bromo- 2 3-F, 7.91 (s,1H), 7.79 pyrazol- 5-Cl (d, 1H), 7.75 (dd, 1-yl 1H), 7.57 (s, 1H), 7.49(dd, 1H), 7.44-7.33 (m, 2H), 7.27 (dd, 1H) A28 0 — imidazo- 2 3-F, 7.71(s, 1H), 7.68 1-yl 5-Cl (s, 1H), 7.51-7.34 (m, 4H), 7.31 (d, 1H), 7.14(s, 1H), 7.03 (s, 1H) A29 0 1,2,4- 2 3-F, 8.58 (s, 1H), 8.01 triazo-5-Cl (s, 1H), 7.82-7.78 1-yl (m, 2H), 7.52-7.38 (m, 3H), 7.32 (d, 1H)A30 1 3-F 3-(5- 2 3-F, 8.80 (s, 1H), 7.55- difluoro- 5-Cl 7.40 (m, 2H),7.18 methyl)- (t, 1H), 7.09 (d, isoxazole 1H), 6.84 (s, 1H), 6.75 (t,1H) A31 1 3-F 5-(3- 2 3-F,  

 7.82 (s, 1H), trifluoro- 5-Cl 7.57-7.51 (m, 2H), methyl)- 7.18 (t, 1H),7.11 isoxazole (d, 1H), 6.88 (s, 1H) A32 1 3-CN 4- 1 5-Cl 8.00 (d, 1H),7.93 (trifluoro- (s, 1H), 7.87 (s, methyl) 1H), 7.73 (d, 1H), pyrazol-7.67-7.55 (m, 3H), 1-yl 6.85 (d, 1H) A33 1 3-CN 4- 2 3-F, 8.03 (s, 1H),7.87 (trifluoro- 5-Cl (s, 1H), 7.78-7.70 methyl) (m, 2H), 7.67-7.60pyrazol- (m, 2H), 7.48 (dd, 1-yl 1H) A34 1 3-CN 4- 2 3,5- 8.03 (s, 1H),7.87 (trifluoro- di-F (s, 1H), 7.75-7.70 methyl) (m, 2H), 7.65-7.60pyrazol- (m, 2H), 7.30 1-yl (ddd, 1H) A35 1 3-F 2-(5- 2 3-F, 7.78 (s,1H), 7.55- difluoro- 5-Cl 7.45 (m, 2H), 7.38 methyl)- (s, 1H), 7.20-7.10oxazole (m, 2H), 6.68 (t, 1H) A36 1 3-OMe 4- 2 3-F, 7.78 (s, 1H), 7.72(trifluoro- 5-Cl (s, 2H), 7.47 (t, methyl) 1H), 7.39 (dd, pyrazol- 1H),7.00-6.91 (m, 1-yl 2H), 3.83 (s, 3H) A37 1 3-F 5-(3- 2 3-CN, 8.15 (d,1H), 8.00 difluoro- 5-Cl (d, 1H), 7.60-7.52 methyl)- (m, 1H), 7.27-7.20isoxazole (m, 1H), 7.15 (dd, 1H), 6.90 (d, 1H), 6.76 (t, 1H) A38 1 3-F5-(3- 2 3-NO₂, 8.41 (d, 1H), 8.20 difluoro- 5-Cl (d, 1H), 7.60-7.54methyl)- (m, 1H), 7.24 (t, isoxazole 1H), 7.12 (d, 1H), 6.94 (d, 1H),6.74 (t, 1H) A39 1 3-F 5-(3- 2 3-F, 5- 8.36 (d, 1H), 7.99 difluoro-SO₂Me (dd, 1H), 7.59 methyl)- (td, 1H), 7.28- isoxazole 7.24 (m, 1H),7.15 (d, 1H), 6.89 (s, 1H), 6.76 (t, 1H), 3.10 (s, 3H) A40 1 3-F 5-(3- 15- 8.61 (d, 1H), 8.22 difluoro- SO₂Me (dd, 1H), 7.59- methyl)- 7.53 (m,1H), 7.25- isoxazole 7.19 (m, 2H), 7.12 (d, 1H), 6.83 (d, 1H), 6.75 (t,1H), 3.08 (s, 3H). A41 1 3-F 5-(3- 1 5-Br 8.13 (d, 1H), 7.82 difluoro-(dd, 1H), 7.51 (dt, methyl)- 1H), 7.14 (ddd, isoxazole 1H), 7.06 (td,1H), 6.95 (d, 1H), 6.78 (s, 1H), 6.75 (t, 1H) A42 1 3-Cl 5-(3- 2 3-F,7.83 (d, 1H), 7.53- difluoro- 5-Cl 7.40 (m, 3H), 7.21 methyl)- (dd, 1H),6.78 (t, isoxazole 1H), 6.69 (s, 1H) A43 0 — 5-(3- 2 3-F, 8.05 (dd, 1H),7.88 difluoro- 5-Cl (d, 1H), 7.59 (dd, methyl)- 1H), 7.56-7.50 (m,isoxazole 1H), 7.39 (dt, 1H), 7.29-7.21 (m, 1H), 6.87 (s, 1H), 6.75 (t,1H) A44 1 3-Br 5-(3- 2 3-F, 7.84 (d, 1H), 7.63 difluoro- 5-Cl (dd, 1H),7.50- methyl)- 7.40 (m, 2H), 7.23 isoxazole (d, 1H), 6.80 (t, 1H), 6.64(s, 1H) A45 0 — 1,2,3- 2 3-F, 7.84 (dd, 1H), 7.63 triazo- 5-Cl (d, 1H),7.60 (s, 2-yl 2H), 7.45-7.28 (m, 4H) A46 1 3-NO₂ 4- 2 3-F, 7.99 (s, 1H),7.89 (trifluoro- 5-Cl (dd, 1H), 7.84- methyl) 7.73 (m, 2H), 7.72-pyrazol- 7.60 (m, 2H), 7.49 1-yl (dd, 1H) A47 1 3-F 5-(3- 1 6-CF₃ 7.87(t, 1H), 7.53- difluoro- 7.48 (m, 1H), 7.38 methyl)- (d, 1H), 7.20-7.12isoxazole (m, 3H), 6.79 (s, 1H), 6.75 (t, 1H) A48 1 3-F 5-(3- 1 6- 7.77(t, 1H), 7.52- difluoro- OCF₂H 7.48 (m, 1H), 7.14 methyl)- (t, 1H), 7.08(d, isoxazole 1H), 6.95 (t, 1H), 6.80 (d, 1H), 6.76 (d, 1H), 6.75 (t,1H), 6.60 (d, 1H) A49 1 3-F 5-(3- 1 3-CN 8.23 (d, 1H), 8.03 difluoro-(d, 1H), 7.60-7.52 methyl)- (m, 1H), 7.25-7.10 isoxazole (m, 3H), 6.87(s, 1H), 6.65 (t, 1H) A50 1 3-F 5-(3- 2 5,6- 7.62-7.55 (m, 1H),difluoro- di-F 7.54-7.49 (m, 1H), methyl)- 7.18-7.10 (m, 2H), isoxazole6.87 (s, 1H), 6.75 (t, 1H), 6.61 (dd, 1H) A51 1 3-F 5-(3- 2 3-Cl, 8.20(s, 1H), 8.01 difluoro- 5-CF₃ (s, 1H), 7.58-7.53 methyl)- (m, 1H), 7.21(t, isoxazole 1H), 7.14 (d, 1H), 6.90 (s, 1H), 6.78 (t, 1H) A53 1 3-F5-(3- 1 3-F 7.86 (d, 1H), 7.54- difluoro- 7.45 (m, 2H), 7.18- methyl)-7.08 (m, 2H), 7.05- isoxazole 7.00 (m, 1H), 6.85 (s, 1H), 6.75 (t, 1H)A54 1 3-Me 4- 2 3-F, 7.80 (s, 1H), 7.79- (trifluoro- 5-Cl 7.70 (m, 2H),7.49- methyl) 7.34 (m, 2H), 7.24 pyrazol- (d, 1H), 7.15 (d, 1-yl 1H),2.18 (s, 3H) A55 1 3-F 5-(3- 1 6- 7.85 (t, 1H), 7.52- difluoro- CHF₂7.45 (m, 1H), 7.36 methyl)- (d, 1H), 7.17-7.05 isoxazole (m, 3H), 6.80(s, 1H), 6.73 (t, 1H), 6.32 (t, 1H) A56 1 3-F 5-(3- 1 4-Et 8.00 (d, 1H),7.49- difluoro- 7.42 (m, 1H), 7.08 methyl)- (t, 1H), 7.05 (d, isoxazole1H), 6.88-6.85 (m, 1H), 6.84 (s, 1H), 6.80 (s, 1H), 6.77 (t, 1H), 2.67(q, 2H), 1.27 (t, 3H) A57 1 3-I 4- 1 3-F, 7.88 (dd, 1H), (trifluoro-5-Cl 7.80 (dd, 2H), methyl) 7.72 (s, 1H), 7.40 pyrazol- (dd, 1H), 7.36-1-yl 7.22 (m, 2H) A58 1 3-F 4- 1 3-F, 7.84 (s, 1H), 7.76 (trifluoro-5-Cl (s, 2H), 7.53-7.45 methyl) (m, 1H), 7.41 pyrazol- (dd, 1H), 7.22-1-yl 7.12 (m, 2H) A59 1 3-Br 4- 1 3-F, 7.81-7.70 (m, 3H), (trifluoro-5-Cl 7.65 (d, 1H), 7.48- methyl) 7.35 (m, 2H), 7.30 pyrazol- (d, 1H)1-yl A60 1 3-F 5-(3- 1 4-Cl 8.30 (d, 1H), 7.60- difluoro- 7.52 (m, 1H),7.23 methyl)- (t, 1H), 7.02 (d, isoxazole 1H), 6.85-6.50 (m, 3H), 6.77(t, 1H) A61 2 3,4- 4- 2 3-F, 7.85 (d, 1H), 7.82- di-Br (trifluoro- 5-Cl7.78 (m, 2H), 7.72 methyl) (s, 1H), 7.41 (dd, pyrazol- 1H), 7.25 (d, 1H)1-yl A62 1 3-F 5-(3- 1 4- 8.29 (d, 1H), 7.58- difluoro- OCF₃ 7.52 (m,1H), 7.22 methyl)- (q, 1H), 7.04 (d, isoxazole 1H), 6.87-6.80 (m, 3H),6.76 (t, 1H) A63 1 3-F 5-(3- 2 3- 7.98 (d, 1H), 7.53 difluoro- NO₂, (q,1H), 7.18 (t, methyl)- 4-Me 1H), 7.14 (d, 1H), isoxazole 6.96 (d, 1H),6.88 (s, 1H), 6.76 (t, 1H), 2.43 (s, 3H) A64 1 3-F 5-(3- 1 5- 8.00 (d,1H), 7.62 difluoro- OCF₃ (dd, 1H), 7.55- methyl)- 7.49 (m, 1H), 7.15isoxazole (t, 1H), 7.10-7.04 (m, 2H), 6.80 (s, 1H), 6.75 (t, 1H) A65 13-F 5-(3- 1 4-Me 7.98 (d, 1H), 7.48 difluoro- (q, 1H), 7.10 (t, methyl)-1H), 7.04 (d, 1H), isoxazole 6.87-6.77 (m, 3H), 6.75 (t, 1H), 2.47 (s,3H) A66 0 — 5-chloro- 2 3-F, 7.81 (s, 1H), 7.62 2-thienyl 5-Cl (d, 1H),7.51 (d, 1H), 7.40-7.22 (m, 2H), 7.19-7.11 (m, 2H), 6.82 (d, 1H) A67 0 —5-cyano- 2 3-F, 7.81 (s, 1H), 7.71 2-thienyl 5-Cl (d, 1H), 7.60-7.49 (m,2H), 7.43 (t, 1H), 7.40-7.31 (m, 2H), 7.20 (d, 1H) A69 0 — 5-chloro- 23-F, 7.77 (s, 1H), 7.50 3-thienyl 5-Cl (d, 1H), 7.44 (d, 1H), 7.41-7.32(m, 1H), 7.32-7.26 (m, 1H), 7.21 (s, 1H), 7.20-7.11 (m, 2H) A70 0 —3-thienyl 2 3-F, 7.75 (s, 1H), 7.58 5-Cl (d, 1H), 7.45 (s, 1H), 7.41 (d,1H), 7.36-7.21 (m, 4H), 7.20 (d, 1H) A71 0 — 4- 2 3-F, 7.81 (s, 1H),7.68 methoxy- 5-Cl (d, 1H), 7.49 (d, 2-thienyl 1H), 7.38-7.24 (m, 2H),7.14 (d, 1H), 7.04 (s, 1H), 6.20 (s, 1H), 3.77 (s, 3H) A72 0 — 2,5- 23-F, 7.74 (s, 1H), 7.44- dimethyl- 5-Cl 7.50 (m, 1H), 7.41- pyrazol-7.30 (m, 3H), 7.25- 3-yl 7.21 (m, 1H), 5.92 (s, 1H), 3.70 (s, 3H), 2.19(s, 3H) A73 0 — 2-methyl- 2 3-F, 7.78 (s, 1H), 7.59- 5- 5-Cl 7.51 (m,1H), 7.45- (trifluoro- 7.36 (m, 3H), 7.30- methyl) 7.22 (m, 1H), 6.41pyrazol- (s, 1H), 3.82 (s, 3-yl 3H) A74 0 — 5-methyl- 2 3-F, 8.45 (d,1H), 7.87 sulfanyl- 5-Cl (d, 1H), 7.59 (d, 1,3,4- 1H), 7.52 (t, 1H),thia- 7.39 (t, 1H), 7.20 diazol-2- (d, 1H), 2.81 (s, yl 3H) A75 05-methyl- 0 3-F, 8.60 (d, 1H), 7.91 sulfonyl- 5-Cl (s, 1H), 7.68-7.551,3,4- (m, 2H), 7.42 (t, thia- 1H), 7.28-7.20 (m, diazol-2- 1H), 3.48(s, 3H) yl A76 1 3-F 5-(3- 2 3-Me, 7.87 (d, 1H), 7.55- difluoro- 6-CN7.50 (m, 1H), 7.20 methyl)- (t, 1H), 7.15 (d, isoxazole 1H), 6.95 (d,1H), 6.88 (s, 1H), 6.75 (t, 1H), 2.35 (s, 3H) A77 1 3-F 5-(3- 1 5- 8.20(d, 1H), 7.55- difluoro- CHF₂ 7.48 (m, 1H), 7.19- methyl)- 7.10 (m, 3H),7.08 isoxazole (d, 1H), 6.78 (s, 1H), 6.75 (t, 1H), 6.65 (t, 1H) A78 13-F 5-(3- 2 4,5- 8.52 (s, 1H), 7.60- difluoro- di-CF₃ 7.54 (m, 1H), 7.45methyl)- (s, 1H), 7.25 (t, isoxazole 1H), 7.12 (d, 1H), 6.85 (s, 1H),6.77 (t, 1H) A79 1 3-F 5-(3- 1 6-CN 7.85 (t, 1H), 7.55- difluoro- 7.50(m, 1H), 7.81 methyl)- (d, 1H), 7.25 (d, isoxazole 1H), 7.18 (t, 1H),7.11 (d, 1H), 6.81 (s, 1H), 6.72 (t, 1H) A80 1 3-F 5-(3- 2 3-CF₃, 8.02(d, 1H), 7.55- difluoro- 6-Cl 7.50 (m, 1H), 7.18 methyl)- (t, 1H), 7.11(d, isoxazole 1H), 7.02 (d, 1H), 6.82 (s, 1H), 6.78 (t, 1H) A81 0 — 4- 23-F, 7.93 (d, 1H), 7.89 (trifluoro- 5-Cl (s, 1H), 7.70 (s, methyl) 1H),7.54 (t, 1H), triazol- 7.50-7.39 (m, 3H) 2-yl A82 0 — 4- 2 3-F, 8.33 (s,1H), 7.81- (trifluoro- 5-Cl 7.89 (m, 2H), 7.57 methyl) (t, 1H), 7.52 (d,triazole- 1H), 7.45 (t, 1H), 1-yl 7.38 (d, 1H) A83 1 6-Br 5-(3- 2 3-F,7.99 (dd, 1H), 7.78 difluoro- 5-Cl (dd, 1H), 7.76 (d, methyl)- 1H), 7.59(dd, 1H), isoxazole 7.34 (t, 1H), 6.76 (s, 1H), 6.75 (t, 1H) A84 1 3-Br5-(3- 2 3-CN, 8.11 (s, 1H), 7.72- difluoro- 5-F 7.66 (m, 2H), 7.47methyl)- (t, 1H), 7.29 (d, isoxazole 1H), 6.74 (t, 1H), 6.70 (s, 1H) A851 3-Cl 5-(3- 2 3-CN, 8.11 (s, 1H), 7.72- difluoro- 5-F 7.68 (m, 1H),7.57- methyl)- 7.48 (m, 2H), 7.28- isoxazole 7.22 (m, 1H), 6.74 (s, 1H),6.74 (t, 1H) A86 1 3-Br 5-(3- 1 4-Cl 8.01 (d, 1H), 7.61 difluoro- (d,1H), 7.43 (t, methyl)- 1H), 7.21 (d, 1H), isoxazole 7.01 (d, 1H), 6.88(s, 1H), 6.77 (t, 1H), 6.57 (s, 1H) A87 1 3-Br 5-(3- 1 4-CN 8.25 (d,1H), 7.67 difluoro- (d, 1H), 7.47 (t, methyl)- 1H), 7.25-7.18 (m,isoxazole 2H), 7.10 (s, 1H), 6.75 (t, 1H), 6.58 (s, 1H) A88 1 3-Br 5-(3-1 5-NO₂ 8.98 (s, 1H), 8.46 difluoro- (d, 1H), 7.70 (d, methyl)- 1H),7.50 (t, 1H), isoxazole 7.28-7.22 (m, 1H), 6.99 (d, 1H), 6.74 (t, 1H),6.60 (s, 1H) A89 1 3-Br 5-(3- 2 3,5- 7.90 (s, 1H), 7.71 difluoro- di-Cl(s, 1H), 7.63 (d, methyl)- 1H), 7.44 (t, 1H), isoxazole 7.26 (d, 1H),6.76 (t, 1H), 6.64 (s, 1H) A90 1 3-Br 5-(3- 1 5-CF₃ 8.36 (s, 1H), 7.88difluoro- (d, 1H), 7.63 (d, methyl)- 1H), 7.43 (t, 1H), isoxazole 7.24(d, 1H), 6.95 (d, 1H), 6.72 (t, 1H), 6.58 (s, 1H) A91 1 3-Cl 5-(3- 14-CN 8.26 (d, 1H), 7.57- difluoro- 7.45 (m, 2H), 7.21- methyl)- 7.16 (m,2H), 7.14 isoxazole (s, 1H), 6.75 (t, 1H), 6.63 (s, 1H) A92 1 3-Cl 5-(3-1 4-Cl 8.00 (d, 1H), 7.50 difluoro- (t, 1H), 7.43 (d, methyl)- 1H), 7.18(d, 1H), isoxazole 7.02 (d, 1H), 6.90 (d, 1H), 6.75 (t, 1H), 6.61 (s,1H) A93 1 6-F 5-(3- 2 3-F, 7.85-7.79 (m, 2H), difluoro- 5-Cl 7.60 (dd,1H), 7.41 methyl)- (dt, 1H), 7.37-7.30 isoxazole (m, 1H), 6.84 (s, 1H),6.77 (t, 1H) A94 1 6-Me 5-(3- 2 3-F, 7.85 (dd, 1H), 7.75 difluoro- 5-Cl(d, 1H), 7.56 (dd, methyl)- 1H), 7.46-7.39 (m, isoxazole 1H), 7.39-7.33(m, 1H), 6.73 (t, 1H), 6.72 (s, 1H), 2.18 (s, 3H) A95 1 6-Cl 5-(3- 23-F, 7.95 (dd, 1H), 7.77 difluoro- 5-Cl (d, 1H), 7.60 (dt, methyl)- 2H),7.40 (t, 1H), isoxazole 6.78 (s, 1H), 6.75 (t, 1H) A96 0 — 4- 2 3-F,7.79-7.72 (m, 2H), methoxy- 5-Cl 7.60 (s, 1H), 7.45 pyrazol- (dd, 1H),7.39-7.31 1-yl (m, 3H), 7.30-7.22 3.71 (s, 3H) A97 0 — 4- 2 3-F, 7.80(s, 1H), 7.69 (trifluoro- 5-Cl (d, 1H), 7.61 (s, methyl) 1H), 7.52-7.48(m, thien-2- 2H), 7.40 (t, 1H), yl 7.31 (t, 1H), 7.20 (d, 1H) A98 1 3-Br5-(3- 1 6-F 7.74 (q, 1H), 7.60 difluoro- (d, 1H), 7.41 (t, methyl)- 1H),7.29-7.20 (m, isoxazole 1H), 6.75 (t, 1H), 6.70 (d, 1H), 6.65- 6.55 (m,2H) A99 1 3-Br 5-(3- 1 4-CF₃ 8.26 (d, 1H), 7.64 difluoro- (dd, 1H), 7.45(t, methyl)- 1H), 7.29-7.18 (m, isoxazole 2H), 7.08 (s, 1H), 6.73 (t,1H), 6.56 (s, 1H) A100 1 3-Br 5-(3- 1 5-Cl 8.04 (s, 1H), 7.63- difluoro-7.57 (m, 2H), 7.41 methyl)- (t, 1H), 7.20 (d, isoxazole 1H), 6.81 (d,1H), 6.76 (t, 1H), 6.57 (s, 1H) A101 1 3-Br 5-(3- 2 3,5- 7.85 (s, 1H),7.58 difluoro- di-F (d, 1H), 7.38 (t, methyl)- 1H), 7.21 (t, 1H),isoxazole 6.93 (d, 1H), 6.84 (t, 1H), 6.75 (s, 1H) A102 1 3-Br 5-(3- 15-CN 8.39 (s, 1H), 7.90 difluoro- (d, 1H), 7.67 (d, methyl)- 1H), 7.46(t, 1H), isoxazole 7.25 d, 1H), 6.95 (d, 1H), 6.73 (t, 1H), 6.58 (s, 1H)A103 1 3-Br 5-(3- 2 3-F, 7.93 (s, 1H), 7.67- difluoro- 5-Br 7.55 (m,2H), 7.45 methyl)- (t, 1H), 7.27 (d, isoxazole 1H), 6.77 (t, 1H), 6.66(s, 1H) A104 1 3-Br 5-(3- 2 3-F, 8.14 (s, 1H), 7.71- difluoro- 5-CF₃7.62 (m, 2H), 7.48 methyl)- (t, 1H), 7.29 (d, isoxazole 1H), 6.75 (t,1H), 6.66 (s, 1H) A105 1 3-Br 5-(3- 2 3-CN, 8.18 (s, 1H), 7.91 difluoro-5-Cl (s, 1H), 7.69 (d, methyl)- 1H), 7.47 (t, 1H), isoxazole 7.29 (d,1H), 6.75 (t, 1H), 6.71 (s, 1H) A106 1 3-Br 5-(3- 1 5-Br 8.15 (s, 1H),7.75 difluoro- (d, 1H), 7.60 d, methyl)- 1H), 7.41 (t, 1H), isoxazole7.20 (d, 1H), 6.77 (d, 1H), 6.76 (t, 1H), 6.56 (s, 1H) A107 1 3-Br 5-(3-1 3-CN 8.26 (s, 1H), 7.95 difluoro- (d, 1H), 7.70 (d, methyl)- 1H), 7.48(t, 1H), isoxazole 7.32 (d, 1H), 7.11 (m, 1H), 6.75 (t, 1H), 6.69 (s,1H) A108 1 3-Cl 5-(3- 1 5-NO₂ 8.98 (s, 1H), 8.49 difluoro- (d, 1H), 7.53(m, methyl)- 2H), 7.24 (d, 1H), isoxazole 7.01 (d, 1H), 6.75 (t, 1H),6.67 (s, 1H) A109 1 3-Cl 5-(3- 2 3,5- 7.90 (s, 1H), 7.73 difluoro- di-Cl(s, 1H), 7.51 (t, methyl)- 1H), 7.45 (d, 1H), isoxazole 7.20 (d, 1H),6.75 (t, 1H), 6.68 (s, 1H) A110 1 3-Cl 5-(3- 1 5-CF₃ 8.35 (s, 1H), 7.89difluoro- (dd, 1H), 7.54- methyl)- 7.42 (m, 2H), 7.20 isoxazole (d, 1H),6.98 (d, 1H), 6.71 (t, 1H), 6.61 (s, 1H) A111 1 3-Cl 5-(3- 1 6-F 7.75(q, 1H), 7.48 difluoro- (t, 1H), 7.42 (d, methyl)- 1H), 7.20 (d, 1H),isoxazole 6.75 (t, 1H), 6.77- 6.70 (m, 1H), 6.65- 6.58 (m, 2H) A112 13-Cl 5-(3- 1 4-CF₃ 8.26 (d, 1H), 7.52 difluoro- (t, 1H), 7.46 (dd,methyl)- 1H), 7.23-7.18 (m, isoxazole 2H), 7.11 (s, 1H), 6.74 (s, 1H),6.60 (s, 1H) A113 1 3-Cl 5-(3- 1 5-Cl 8.05 (s, 1H), 7.66 difluoro- (d,1H), 7.49 (t, methyl)- 1H), 7.44 (d, 1H), isoxazole 7.19 (d, 1H) 6.86(d, 1H), 6.75 (t, 1H), 6.51 (s, 1H) A114 1 3-Cl 5-(3- 2 3,5- 7.86 (s,1H), 7.47- difluoro- di-F 7.40 (m, 2H), 7.21 methyl)- (t, 1H), 7.90 (d,isoxazole 1H), 6.83 (t, 1H), 6.77 (s, 1H) A115 1 3-Cl 5-(3- 1 5-CN 8.38(s, 1H), 7.91 difluoro- (d, 1H), 7.55-7.45 methyl)- (m, 2H), 7.20 (d,isoxazole 1H), 7.00 (d, 1H), 6.74 (t, 1H), 6.64 (s, 1H) A116 1 3-Cl5-(3- 2 3-F, 7.91 (s, 1H), 7.60 difluoro- 5-Br (d, 1H), 7.52-7.42methyl)- (m, 2H), 7.20 (d, isoxazole 1H), 6.75 (t, 1H), 6.70 (s, 1H)A117 1 3-Cl 5-(3- 2 3-F, 8.12 (s, 1H), 7.67 difluoro- 5-CF₃ (d, 1H),7.58-7.45 methyl)- (m, 2H), 7.28-7.22 isoxazole (m, 1H), 6.74 (t, 1H),6.70 (s, 1H) A118 1 3-Cl 5-(3- 2 3-CN, 8.19 (s, 1H), 7.92 difluoro-5-CF₃ (s, 1H), 7.58-7.49 methyl)- (m, 2H), 7.29-7.21 isoxazole (m, 1H),6.75 (s, 1H), 6.75 (t, 1H) A119 1 3-Cl 5-(3- 1 5-Br 8.14 (s, 1H), 7.77difluoro- (d, 1H), 7.49 (t, methyl)- 1H), 7.43 (d, 1H), isoxazole 7.18(d, 1H), 6.80 (d, 1H), 6.76 (t, 1H), 6.61 (s, 1H) A120 1 3-Cl 5-(3- 13-CN 8.25 (d, 1H), 7.97 difluoro- (d, 1H), 7.58-7.45 methyl)- (m, 2H),7.30-7.23 isoxazole (m, 1H), 7.12-7.08 (m, 1H), 6.74 (t, 1H), 6.73 (s,1H) A121 0 — 3- 2 3-F, 7.89 (s, 1H), 7.80- (trifluoro- 5-Cl 7.71 (m,2H), 7.49- methyl) 7.42 (m, 2H), 7.40 pyrazole- (t, 1H), 7.32 (d, 1-yl1H), 6.56 (s, 1H) A122 0 — 5- 2 3-F, 7.82 (s, 1H), 7.60- (trifluoro-5-Cl 7.53 (m, 2H), 7.51 methyl) (d, 1H), 7.41-7.32 pyrazole- (m, 3H),6.70 (s, 1-yl 1H) A123 0 — 3,5-bis 2 3-F, 7.84 (s, 1H), 7.61 (trifluoro-5-Cl (t, 1H), 7.52 (d, methyl) 1H), 7.45 (d, 1H), pyrazol- 7.43-7.35 (m,2H), 1-yl 6.96 (s, 1H) A124 1 3-F 5-(3- 2 4-Cl, 8.60 (s, 1H), 7.55-difluoro- 5- 7.50 (m, 1H), 7.20 methyl)- CO₂Et (t, 1H), 7.12 (s,isoxazole 1H), 7.05 (d, 1H), 6.80 (d, 1H), 6.75 (t, 1H), 4.37 (q, 2H),1.38 (t, 3H) A126 0 — 5-(3- 2 3-F, 8.20 (d, 1H), 7.75 methyl- 5-Cl (s,1H), 7.66 (t, 1,2,4- 1H), 7.53 (dd, 1H), oxadia- 7.44 (t, 1H), 7.30zole) (d, 1H), 2.38 (s, 3H) A128 0 — 3-(5- 2 3-F, 8.16 (d, 1H), 7.74methyl- 5-Cl (s, 1H), 7.56 (t, 1,2,4- 1H), 7.50 (d, 1H), oxadia- 7.42(t, 1H), 7.30 zole) (d, 1H), 2.55 (s, 3H) A129 0 — 2-(4- 2 3-F, 8.35 (d,1H), 7.80 methyl- 5-Cl (s, 1H), 7.53 (dd, thiazole) 1H), 7.41 (t, 1H),7.35 (t, 1H), 7.18 (d, 1H), 6.87 (s, 1H), 2.46 (s, 3H) A130 0 — 2-(5- 23-F, 8.12 (d, 1H), 7.75 methyl- 5-Cl (s, 1H), 7.60 (t, 1,2,4- 1H), 7.55(dd, 1H), oxadia- 7.42 (t, 1H), 7.31 zole) (d, 1H), 2.49 (s, 3H) A131 0— 4-(5- 2 3-F, 7.76 (d, 1H), 7.62 methyl- 5-Cl (d, 1H), 7.55 (t,thiadia- 1H), 7.41 (t, 1H), zole) 7.37 (dd, 1H), 7.31 (d, 1H), 2.58 (s,3H) A132 0 — 2-(1,3,4- 2 3-F, 8.40 (s, 1H), 8.17 oxadia- 5-Cl (d, 1H),7.75 (s, zole) 1H), 7.62 (t, 1H), 7.55 (dd, 1H), 7.44 (t, 1H), 7.31 (d,1H) A137 1 3-F 5-(3- 2 3- 8.25 (d, 1H), 7.55- difluoro- CO₂Et, 7.50 (m,1H), 7.18 methyl)- 6-Cl (t, 1H), 7.12 (d, isoxazole 1H), 6.97 (d, 1H),6.81 (s, 1H), 6.75 (t, 1H), 4.38 (q, 2H), 1.40 (t, 3H) A142 0 — 2-(5- 23-F, 8.52 (d, 1H), 7.99 difluoro- 5-Cl (s, 1H), 7.61 (d, methyl- 1H),7.58-7.51 (m, sulfanyl)- 1H), 7.45-7.37 (m, 1,3,4- 1H), 7.42 (t, 1H),thiadia- 7.22 (d, 1H) zole A143 0 — 3- 2 3-F, 8.86 (br, 1H), 7.81methyl- 5-Cl (s, 1H), 7.65-7.58 imidazo- (m, 1H), 7.48 (d, 4-yl 1H),7.42-7.37 (m, 2H), 7.23 (t, 2H), 3.80 (s, 3H) A144 0 — 2- 2 3-F, 7.98(d, 1H), 7.29 methyl- 5-Cl (s, 1H), 7.46 (dd, pyrazol- 1H), 7.35-7.24(m, 3-yl 3H), 7.17 (d, 1H), 6.55 (s, 1H), 3.90 (s, 3H) A145 0 — 5-iso- 23-F, 8.42 (s, 1H), 7.82- thiazole 5-Cl 7.75 (m, 2H), 7.58- 7.51 (m, 2H),7.45 (t, 1H), 7.36 (t, 1H), 7.25 (d, 1H) A146 0 — 5- 2 3-F, 8.73 (s,1H), 8.12 thiazole 5-Cl (s, 1H), 7.80 (s, 1H), 7.69 (d, 1H), 7.49 (d,1H), 7.42 (t, 1H), 7.32 (t, 1H), 7.21 (d, 1H) A147 0 — 2- 2 3-F, 8.42(d, 1H), 7.88 thiazole 5-Cl (s, 1H), 7.73 (s, 1H), 7.55 (d, 1H), 7.46(t, 1H), 7.41- 7.32 (m, 2H), 7.21 (d, 1H) A148 0 — 3-furan 2 3-F, 7.78(d, 2H), 7.56 5-Cl (d, 1H), 7.47 (d, 1H), 7.39 (s, 1H), 7.36-7.21 (m,2H), 7.16 (d, 1H), 6.69 (s, 1H) A149 0 — 2-furan 2 3-F, 7.98-7.88 (m,1H), 5-Cl 7.82 (s, 1H), 7.51 (d, 1H), 7.41 (s, 1H), 7.35-7.26 (m, 2H),7.20-7.12 (m, 1H), 6.73 (s, 1H), 6.41 (s, 1H) A154 1 3-F 5-(3- 2 5- 8.25(d, 1H), 7.50 difluoro- CO₂Et, (q, 1H), 7.13 (t, methyl)- 6-Me 1H), 7.09(d, 1H), isoxazole 6.84-6.78 (m, 2H), 6.75 (t, 1H), 4.37 (q, 2H), 2.61(s, 3H), 1.37 (t, 3H) A156 1 3-F 5-(3- 2 4- 7.75 (s, 1H), 7.55-difluoro- CO₂Et, 7.48 (m, 1H), 7.48 methyl)- 6-Br (s, 1H), 7.17 (t,isoxazole 1H), 7.10 (d, 1H), 6.84 (s, 1H), 6.76 (t, 1H), 4.42 (q, 2H),1.40 (t, 3H) A158 1 3-CF₃ 4- 2 3-F, 7.83-7.78 (m, 2H), (trifluoro- 5-Cl7.78-7.67 (m, 3H), methyl) 7.60 (dd, 1H), 7.41 pyrazol- (dd, 1H) 1-ylA159 1 3-Cl 4- 2 3-F, 7.81-7.71 (m, 3H), (trifluoro- 5-Cl 7.53-7.42 (m,2H), methyl) 7.40 (dd, 1H), 7.29 pyrazol- (dd, 1H) 1-yl A160 1 3-CN5-(3- 2 3,5- 7.81-7.71 (m, 2H), difluoro- di-F 7.66 (t, 1H), 7.55methyl)- (dd, 1H), 7.38 isoxazole (ddd, 1H), 6.98 (s, 1H), 6.80 (t, 1H)A161 1 3-CN 5-(3- 1 5-Cl 8.03 (d, 1H), 7.78- difluoro- 7.68 (m, 2H),7.65 methyl)- (t, 1H), 7.51 (dd, isoxazole 1H), 6.98 (d, 1H), 6.89 (s,1H), 6.79 (t, 1H) A162 1 3-CN 5-(3- 2 3-F, 7.82 (d, 1H), 7.77 difluoro-5-Cl (dd, 1H), 7.67 (t, methyl)- 1H), 7.59-7.54 (m, isoxazole 2H), 6.98(s, 1H), 6.80 (t, 1H) A163 0 — 3-(5- 2 3-F, 7.97 (d, 1H), 7.82 difluoro-5-Cl (s, 1H), 7.58-7.50 methyl)- (m, 2H), 7.38 (t, isoxazole 1H), 7.22(d, 1H), 6.95 (s, 1H), 6.73 (t, 1H) A167 0 — pyrazol- 2 3-F, 7.86 (s,1H), 7.82- 1-yl 5-Cl 7.71 (m, 2H), 7.60 (s, 1H), 7.42 (d, 1H), 7.40-7.32(m, 2H), 7.32-7.22 (m, 1H), 6.31 (s, 1H) A168 0 — (4- 2 3-F, 7.90 (d,1H), 7.85 difluoro- 5-Cl (s, 1H), 7.71 (s, methyl)- 1H), 7.52 (t, 1H),triazol- 7.49-7.37 (m, 3H), 2-yl 6.75 (t, 1H) A169 0 — (4- 2 3-F, 8.25(s, 1H), 7.84 difluoro- 5-Cl (d, 1H), 7.80 (s, methyl)- 1H), 7.55 (t,1H), triazol- 7.52-7.40 (m, 2H), 1-yl 7.36 (d, 1H), 6.88 (t, 1H) A170 0— 2(5- 2 3-F, 8.10 (d, 1H), 7.65 difluoro- 5-Cl (s, 1H), 7.52 (t,methyl)- 1H), 7.45 (d, 1H), oxazole 7.32 (t, 1H), 7.25- 7.20 (m, 2H),6.55 (t, 1H) A171 1 4-Cl thiazol- 2 3-F, 8.43 (s, 1H),7.90 2-yl 5-Cl (d,1H), 7.83 (s, 1H), 7.55 (d, 1H), 7.43-7.37 (m, 2H), 7.16 (d, 1H) A172 13-F 5-(3- 2 5-Cl, 7.85 (d, 1H), 7.57- difluoro- 6-CN 7.52 (m, 1H), 7.26-methyl)- 7.18 (m, 2H), 7.10 isoxazole (d, 1H), 6.85 (d, 1H), 6.67 (t,1H) A173 1 3-F 5-(3- 2 3-CN, 8.19 (s, 1H), 7.56- difluoro- 4-Cl 7.52 (m,1H), 7.33 methyl)- (s, 1H), 7.21 (t, isoxazole 1H), 7.07 (d, 1H), 6.84(d, 1H), 6.76 (t, 1H) A174 1 3-F thiazol- 2 3-F, 7.82 (s, 1H), 7.75 2-yl5-Cl (s, 1H), 7.50-7.39 (m, 3H), 7.14 (t, 1H), 7.09 (d, 1H) A175 1 3-Brthiazol- 2 3-F, 7.84 (dd, 2H), 7.61 2-yl 5-Cl (d, 1H), 7.42 (s, 1H),7.41-7.35 (m, 2H), 7.25-7.20 (m, 1H) A176 1 3-Cl thiazol- 2 3-F,7.88-7.80 (m, 2H), 2-yl 5-Cl 7.48-7.41 (m, 3H), 7.38 (d, 1H), 7.21- 7.15(m, 1H)

BIOLOGICAL EXAMPLES

Seeds of a variety of test species are sown in standard soil in pots(Lolium perenne (LOLPE), Solanum nigrum (SOLNI), Amaranthus retoflexus(AMARE), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), Ipomoeahederacea (IPOHE)). After cultivation for one day (pre-emergence) orafter 8 days cultivation (post-emergence) under controlled conditions ina glasshouse (at 24/16° C., day/night; 14 hours light; 65% humidity),the plants are sprayed with an aqueous spray solution derived from theformulation of the technical active ingredient in acetone/water (50:50)solution containing 0.5% Tween 20 (polyoxyethelyene sorbitanmonolaurate, CAS RN 9005-64-5). Compounds are applied at 500 g/ha unlessotherwise stated. The test plants are then grown in a glasshouse undercontrolled conditions in a glasshouse (at 24/16° C., day/night; 14 hourslight; 65% humidity) and watered twice daily. After 13 days for pre andpost-emergence, the test is evaluated for the percentage damage causedto the plant. The biological activities are shown in the following tableon a five point scale (5=81-100%; 4=61-80%; 3=41-60%; 2=21-40%;1=0-20%).

TABLE B1 Post-emergence Test Rate Compound (g/ha) AMARE SOLNI SETFALOLPE ECHCG IPOHE A1 500 5 5 5 5 5 5 A2 500 5 5 5 5 5 4 A3 500 2 3 4 1 11 A4 500 5 5 3 1 1 1 A6 500 4 5 5 4 5 3 A7 500 2 5 5 2 4 2 A8 500 2 5 41 2 1 A9 500 5 5 5 5 5 4 A10 500 5 5 5 5 5 5 A12 500 5 5 5 5 5 5 A141000 5 5 5 5 5 4 A15 1000 1 4 3 1 2 2 A16 1000 4 5 5 5 5 5 A17 1000 5 55 5 5 5 A18 250 3 3 3 2 4 2 A19 1000 5 5 5 5 5 5 A20 1000 5 5 4 4 4 5A21 1000 4 3 4 3 4 3 A22 1000 4 4 3 2 2 3 A23 1000 5 5 5 5 5 5 A24 10004 4 4 3 4 3 A25 1000 5 5 5 5 4 4 A26 1000 5 5 5 3 5 3 A27 250 4 5 5 2 52 A28 1000 5 4 1 1 1 1 A29 1000 4 4 2 1 1 2 A30 1000 5 5 5 5 5 5 A311000 5 5 5 5 5 5 A32 1000 5 5 5 5 5 5 A33 1000 5 5 5 5 5 5 A34 1000 5 55 5 5 5 A35 1000 5 5 4 1 1 2 A36 1000 5 5 5 4 4 2 A37 1000 5 5 5 4 4 5A38 1000 5 5 1 1 1 1 A39 1000 3 3 1 1 1 1 A40 1000 3 4 1 1 1 1 A41 10005 5 5 5 5 5 A42 250 5 5 5 5 4 4 A43 1000 5 5 5 5 4 4 A44 1000 5 5 5 5 55 A46 1000 5 5 4 3 3 2 A47 1000 3 3 1 1 1 1 A48 1000 5 5 2 1 1 2 A491000 5 5 2 1 3 3 A50 1000 3 5 3 1 2 1 A51 1000 4 5 1 1 1 1 A54 1000 3 55 4 3 1 A55 1000 5 5 2 1 1 1 A57 1000 5 5 4 1 1 2 A58 1000 5 5 5 5 4 5A59 1000 5 5 5 4 3 5 A60 1000 4 4 2 1 1 2 A61 1000 5 5 2 1 1 2 A62 10004 3 3 2 3 3 A66 1000 5 5 2 1 3 2 A69 1000 3 4 3 1 4 2 A70 1000 3 4 2 1 31 A71 1000 4 5 2 1 1 1 A76 250 2 4 1 1 1 3 A77 250 5 5 5 2 2 1 A78 10003 4 1 1 1 1 A80 1000 5 5 1 1 1 1 A81 1000 5 4 4 1 4 2 A82 1000 5 5 5 5 45 A83 1000 5 4 4 4 4 2 A84 1000 5 5 5 5 5 5 A85 1000 5 5 5 5 5 5 A861000 4 4 4 4 4 4 A87 1000 4 4 5 3 3 3 A88 1000 5 4 4 3 4 2 A89 1000 5 45 3 4 4 A90 1000 5 4 5 4 4 4 A91 1000 4 4 4 4 4 4 A92 1000 4 4 4 4 4 4A93 1000 5 3 5 3 4 3 A94 1000 4 4 3 2 2 1 A95 1000 4 4 4 3 3 1 A97 10005 4 5 3 4 4 A98 1000 4 4 5 3 4 3 A99 1000 5 4 4 3 4 2 A100 250 5 NT 5 NT5 2 A101 1000 5 5 5 4 4 5 A102 1000 5 5 5 4 4 5 A103 1000 5 5 5 5 4 5A104 1000 4 5 4 3 4 4 A105 1000 5 5 5 4 4 5 A106 1000 5 5 5 5 4 4 A1071000 5 5 5 3 4 4 A108 1000 5 4 4 4 4 3 A109 1000 5 5 5 3 4 4 A110 1000 55 5 4 4 4 A111 1000 5 5 5 4 4 4 A112 1000 4 4 4 3 3 3 A113 1000 5 4 5 54 5 A114 1000 5 5 5 4 4 5 A115 1000 5 5 5 4 4 5 A116 1000 5 5 5 5 4 5A117 1000 5 4 4 4 4 5 A118 1000 5 5 5 5 5 5 A119 1000 5 5 5 5 4 5 A1201000 5 5 5 3 4 4 A121 1000 4 4 3 1 3 2 A159 1000 5 5 5 4 3 4 A160 1000 55 5 5 5 5 A161 1000 5 5 5 5 5 5 A162 1000 5 5 5 5 4 5 A163 250 5 NT 5 NT5 3 A169 250 5 NT 5 NT 5 5 NT = Not Tested

TABLE B2 Pre-emergence Test Rate Compound (g/ha) AMARE SOLNI SETFA LOLPEECHCG IPOHE A1 500 5 5 5 5 5 5 A2 500 5 4 5 4 5 2 A3 500 3 3 3 1 3 1 A4500 3 3 2 1 2 1 A6 500 5 5 5 4 4 2 A7 500 5 5 4 1 4 1 A8 500 5 4 3 1 2 1A9 500 5 5 5 4 5 3 A10 500 5 5 5 5 5 5 A12 500 5 5 5 5 5 5 A14 1000 5 55 5 5 3 A15 1000 5 4 5 3 5 1 A16 1000 5 5 5 5 5 5 A17 1000 5 5 5 5 5 5A18 250 5 5 5 1 5 1 A19 1000 5 5 5 5 5 5 A20 1000 4 3 5 5 5 3 A21 1000 52 5 4 5 2 A22 1000 5 1 3 1 3 1 A23 1000 5 4 5 5 5 5 A24 1000 5 3 5 4 5 3A25 1000 5 5 5 5 5 5 A26 1000 5 5 5 5 5 4 A27 250 5 5 4 3 5 1 A28 1000 31 1 1 1 1 A29 1000 5 3 4 1 1 1 A30 1000 5 5 5 5 5 5 A31 1000 5 5 5 5 5 5A32 1000 5 5 5 4 5 5 A33 1000 5 5 5 4 5 2 A34 1000 5 5 5 5 5 5 A35 10003 5 5 1 5 1 A36 1000 5 5 5 3 5 5 A37 1000 5 5 5 5 5 5 A38 1000 4 1 1 1 11 A39 1000 5 1 1 1 1 1 A40 1000 2 1 1 1 1 1 A41 1000 5 5 5 5 5 3 A42 2505 4 5 5 5 3 A43 1000 5 5 5 5 5 4 A44 1000 5 5 5 5 5 5 A46 1000 4 1 5 1 41 A47 1000 1 1 1 1 1 1 A48 1000 1 1 1 1 1 1 A49 1000 5 5 5 1 3 1 A501000 4 4 4 1 1 1 A51 1000 1 1 1 1 1 1 A54 1000 5 5 5 5 3 1 A55 1000 2 24 1 1 1 A57 1000 5 4 5 1 1 NT A58 1000 5 5 5 5 5 5 A59 1000 5 5 5 4 2 2A60 1000 5 1 1 1 2 1 A61 1000 1 1 2 1 1 1 A62 1000 4 1 1 1 1 1 A69 10003 1 1 1 1 1 A70 1000 2 1 1 1 1 1 A71 1000 5 1 1 1 1 1 A77 250 5 4 5 2 21 A78 1000 1 1 2 1 1 1 A80 1000 2 1 1 1 1 1 A81 1000 5 3 4 1 4 2 A821000 5 4 5 5 5 5 A83 1000 4 1 2 1 2 1 A84 1000 5 4 5 5 5 5 A85 1000 5 55 5 5 5 A86 1000 4 2 5 4 5 1 A87 1000 4 3 5 4 4 1 A88 1000 5 4 5 4 5 1A89 1000 4 2 4 2 4 3 A90 1000 4 4 5 5 5 3 A91 1000 4 3 5 4 5 4 A92 10004 2 5 5 1 4 A93 1000 4 4 4 3 4 3 A94 1000 4 2 2 2 3 1 A95 1000 4 1 3 1 41 A97 1000 4 2 4 2 3 2 A98 1000 4 3 5 3 5 1 A99 1000 5 1 4 3 4 1 A100250 5 NT 5 NT 2 1 A101 1000 5 4 5 5 5 5 A102 1000 5 4 5 5 5 4 A103 10005 3 5 5 5 5 A104 1000 4 2 5 4 4 4 A105 1000 5 5 5 5 5 5 A106 1000 4 3 55 5 3 A107 1000 5 2 5 2 4 3 A108 1000 4 4 5 5 5 1 A109 1000 4 3 4 2 2 1A110 1000 5 4 5 4 4 4 A111 1000 5 4 5 4 5 1 A112 1000 5 2 5 3 4 1 A1131000 5 4 5 5 5 4 A114 1000 5 4 5 5 5 5 A115 1000 5 4 5 5 5 5 A116 1000 54 5 5 5 4 A117 1000 5 2 5 4 4 5 A118 1000 5 4 5 5 5 4 A119 1000 5 4 5 55 4 A120 1000 5 4 5 2 5 3 A121 1000 4 1 3 1 4 1 A126 250 5 NT 3 NT 4 1A159 1000 5 5 5 5 5 2 A160 1000 5 4 5 5 5 5 A161 1000 5 4 5 5 5 5 A1621000 5 4 5 5 5 5 A163 250 5 NT 5 NT 4 1 A169 250 5 NT 5 NT 5 5 NT = NotTested

BIOLOGICAL EXAMPLES

TABLE B3 Comparative Test TEST Compound Rate GLYMA AMARE 1 PYRIMIDINECOMPARATOR WO2015/108779 CMP 55

500 250  90  70 100 100 A30

500 250   0   0 100 100 2 PYRIMIDINE COMPARATOR WO2015/108779 CMP 144

500 250  90  10 100 100 A1

500 250   0   0 100 100 A37

500 250   0   0 100 100 3 PYRIMIDINE COMPARATOR WO2015/108779 CMP 145

500 250  40  10 100 100 A20

500 250   0   0 100 100 4 PYRIMIDINE COMPARATOR WO2015/089003 CMP 58

500 250 100  90 100 100 A33

500 250   0   0 100 100 5 PYRIMIDINE COMPARATOR

500 250 100  90 100 100 A162

500 250   0   0 100 100

Seeds of a variety of test species were sown in standard soil in pots.After cultivation for one day (pre-emergence) under controlledconditions in a glasshouse (at 24/16° C., day/night; 14 hours light; 65%humidity), the plants were sprayed with an aqueous spray solutionderived from the formulation of the technical active ingredient in 0.6ml acetone and 45 ml formulation solution containing 10.6% Emulsogen EL(Registry number 61791-12-6), 42.2% N-methyl pyrrolidone, 42.2%dipropylene glycol monomethyl ether (CAS RN 34590-94-8) and 0.2% X-77(CAS RN 11097-66-8). The test plants were then grown in a glasshouseunder controlled conditions in a glasshouse (at 24/16° C., day/night; 14hours light; 65% humidity) and watered twice daily. After 21 days thetest was evaluated (100=total damage to plant; 0=no damage to plant).

Test Plants:

Weed species: Amaranthus retroflexus (AMARE)

Crops: Soybean (Glycine max (GLYMA))

The results demonstrate that the pyridine compounds of the presentinvention exhibit much reduced herbicidal damage to the crop (soybean)compared to the pyrimidine compounds of the prior art whilst weed(AMARE) control remains comparable.

1. A compound of Formula (I):

or an agronomically acceptable salt thereof, wherein Q is a 5-memberedaromatic heterocyclic ring which is optionally substituted by 1 or 2 R³substituents independently selected from the group consisting ofC₁-C₄alkyl, C₂-C₄alkenyl, C₂-C₄alkynyl, cyclopropyl, C₁-C₄haloalkyl,C₁-C₂alkoxy-, C₁-C₂haloalkoxy-, halogen, —C(O)C₁-C₄alkyl, NO₂, —CH₂CN,—CN and —S(O)_(p)C₁-C₄alkyl; each R¹ is independently selected from thegroup consisting of halogen, —CN, nitro, C₁-C₄alkyl, C₂-C₄alkenyl,C₂-C₄alkynyl, C₁-C₄haloalkyl, C₁-C₄alkoxy-, C₁-C₄haloalkoxy- and—S(O)_(p)C₁-C₄alkyl; each R² is independently selected from the groupconsisting of halogen, —CN, NO₂, C₁-C₄alkyl, C₁-C₄haloalkyl,C₃-C₆cycloalkyl C₂-C₄alkenyl, C₂-C₄alkynyl, —S(O)_(p)C₁-C₄alkyl,C₁-C₄alkoxy, —C(O)C₁-C₄alkyl, —C(O)OC₁-C₄alkyl and C₁-C₄haloalkoxy; m=0,1 or 2; n=0, 1 or 2; and p=0, 1 or
 2. 2. The compound of Formula (I)according to claim 1, wherein Q is selected from the group consisting of

wherein R³ is selected from the group consisting of hydrogen,C₁-C₄alkyl, C₂-C₄alkenyl, C₂-C₄alkynyl, cyclopropyl, C₁-C₂haloalkyl,C₁-C₂alkoxy-, C₁-C₂haloalkoxy-, halogen, —C(O)C₁-C₄alkyl, NO₂, —CH₂CN,—CN and —S(O)_(p)C₁-C₄alkyl; and R^(3a) is hydrogen or C₁-C₂ alkyl withthe proviso that Q is not 1,3,4-oxadiazol-2-yl or a C-linked tetrazolyland wherein if Q is 2-thienyl or 2-furyl then said 2-thienyl or 2-furylis substituted by 1 or 2 R³ independently selected from the groupconsisting of C₁-C₂haloalkyl, halogen and —CN.
 3. The compound ofFormula (I) according to claim 1, wherein Q is selected from the groupconsisting of Q19, Q20 and Q34.
 4. The compound of Formula (I) accordingto claim 1, wherein Q is Q20.
 5. The compound according to claim 1,wherein n is 1 and R¹ is fluorine.
 6. The compound according to claim 5,wherein R¹ is 3-fluoro.
 7. The compound according to claim 1, wherein mis 1 or 2 and R² is independently selected from the group consisting offluorine, nitro, cyano and trifluoromethyl.
 8. The compound according toclaim 1, wherein R³ is difluoromethyl or trifluoromethyl.
 9. Aherbicidal composition comprising a compound according to claim 1 and anagriculturally acceptable formulation adjuvant.
 10. The herbicidalcomposition according to claim 9, further comprising at least oneadditional pesticide.
 11. The herbicidal composition according to claim10, wherein the additional pesticide is a herbicide or herbicidesafener.
 12. A method of controlling weeds at a locus comprisingapplication to the locus of a weed controlling amount of a compositionaccording to claim
 9. 13. Use of a compound of Formula (I) as defined inclaim 1 as a herbicide.